APLIKASI M–COMMERCE BERBASIS ANDROID PADA ZONA KOMPUTER BANJARNEGARA

OpenAIRE

Andi Dwi Riyanto; Khatirudin Ma’arif

2016-01-01

Transaksi bisnis jual beli e-Commerce saat ini memasuki mulai bergeser memanfaatkan perangkat gadget/smartphone. Perkembangan inilah yang disebut dengan m-Commerce, yakni memanfaatkan smartphone untuk melakukan transaksi jual beli barang. Zona Komputer Banjarnegara telah memiliki website e-Commerce. Namun demikian, Zona Komputer berinovasi untuk menjadi yang terdepan dalam melayani konsumen yakni dengan membuat m-Commerce untuk memudahkan pelanggan dalam transaksi jual beli. Metode pengembang...

Programa de manejo integral de zonas costeras de Nicaragua (MAIZCo

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Fátima Vanegas Zúñiga

2016-03-01

Full Text Available El Plan de Acción para el Manejo de las Zonas Costeras de Nicaragua fue formulado durante la primera fase del programa “Manejo Integral de las Zonas Costeras de Nicaragua” (MAIZCo. La agencia ejecutora de la primera fase fue la Dirección General del Ambiente (DGA del Ministerio del Ambiente y Recursos Naturales (MARENA. Las estrategias y propuestas de acciones inmediatas formuladas en el Plan de Acción están basadas en un marco conceptual y un diagnóstico de las potencialidades y problemática de la Zona Costera. Tanto el marco conceptual como el diagnostico fueron desarrollados en un intenso proceso de interacción con los actores sustantivos. Una serie de entrevistas y talleres a nivel local, regional y nacional fueron organizados. Un primer paso incluyó la definición de los siguientes dos principios guías para el Manejo Integral de las Zonas Costeras en Nicaragua. El objetivo general del plan es facilitar un uso sostenible de los recursos naturales en las zonas Costeras de Nicaragua para el beneficio de toda la sociedad. Además, como objetivos específicos se considera contribuir al crecimiento económico; mantener la integridad de los ecosistemas costeros; contribuir a una distribución equitativa de los bienes y servicios producidos por los recursos naturales; y facilitar un efectivo y eficiente manejo. El diagnóstico de las zonas costeras incluyó: Nicaragua tiene extensivos recursos naturales en el área costera, los cuales podrían –pero no- jugar un substancial rol en el desarrollo social y económico de Nicaragua. La problemática general no es la degradación de los ecosistemas costeros, pero si en general los recursos están subexplotados y los beneficios no están bien distribuidos. Un uso indiscriminado, sin embargo, podría significar en un futuro inmediato la sobreexplotación de ecosistemas específicos (ejemplo: áreas de manglares en la costa Pacífica y especies (ejemplos: la langosta en la costa Atl

las Zonas Ribereñas

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D. Granados-Sánchez

2006-01-01

Full Text Available Muchas especies de plantas tienen fuertes asociaciones con las zonas riparias, pues crecen a lo largo de las márgenes del agua. El microclima húmedo de la zona riparia y la humedad del suelo, creados tanto por el afloramiento de agua como por el agua del terreno cercana a la superficie, tiende a hacerlos hábitats favorables para muchos anfibios y algunos mamíferos pequeños. Comenzando en el borde del agua y avanzando progresivamente hacia el interior del bosque, frecuentemente se definen bandas sucesivas de vegetación, mediante cambios muy pequeños en la topografía. Estos ecosistemas tienen muchos atributos que realzan su diversidad biológica: límites, patrones sucesionales, disposición vertical en estratos y microhábitats especiales definidos por sus rasgos físicos. Pececillos de río, ranas y ardillas, algas, platanus, sauces, pinos y encinos, todos ellos prosperan conjuntamente a lo largo de las playas de las corrientes de agua.

Affinity purification and partial characterization of the zonulin/zonula occludens toxin (Zot) receptor from human brain.

Science.gov (United States)

Lu, R; Wang, W; Uzzau, S; Vigorito, R; Zielke, H R; Fasano, A

2000-01-01

The intercellular tight junctions (TJs) of endothelial cells represent the limiting structure for the permeability of the blood-brain barrier (BBB). Although the BBB has been recognized as being the interface between the bloodstream and the brain, little is known about its regulation. Zonulin and its prokaryotic analogue, zonula occludens toxin (Zot) elaborated by Vibrio cholerae, both modulate intercellular TJs by binding to a specific surface receptor with subsequent activation of an intracellular signaling pathway involving phospholipase C and protein kinase C activation and actin polymerization. Affinity column purification revealed that human brain plasma membrane preparations contain two Zot binding proteins of approximately 55 and approximately 45 kDa. Structural and kinetic studies, including saturation and competitive assays, identified the 55-kDa protein as tubulin, whereas the 45-kDa protein represents the zonulin/Zot receptor. Biochemical characterization provided evidence that this receptor is a glycoprotein containing multiple sialic acid residues. Comparison of the N-terminal sequence of the zonulin/Zot receptor with other protein sequences by BLAST analysis revealed a striking similarity with MRP-8, a 14-kDa member of the S-100 family of calcium binding proteins. The discovery and characterization of this receptor from human brain may significantly contribute to our knowledge on the pathophysiological regulation of the BBB.

New method for culture of zona-included or zona-free embryos: the Well of the Well (WOW) system.

Science.gov (United States)

Vajta, G; Peura, T T; Holm, P; Páldi, A; Greve, T; Trounson, A O; Callesen, H

2000-03-01

Culture of mammalian zygotes individually and in small groups results in lower developmental rates than culture of large groups. Zona-free zygotes also have impaired developmental potential in current culture systems. This paper describes a new approach to resolve the problems, the Well of the Well (WOW) system. Small wells (WOWs) were formed in four-well dishes by melting the bottom with heated steel rods. The WOWs were then rinsed, the wells were filled with medium, and the embryos were placed into the WOWs. To test the value of the WOW system a 3 x 3 factorial experiment was performed. Bovine presumptive zygotes were cultured from day 1 to day 7 (day 0: day of insemination) using three modules (single embryos, embryo groups of five, or single zona-digested embryos) and three different culture systems (400 microl medium, 200 microl drops, or WOWs). An additional control group consisted of 40 to 50 embryos cultured in 400 microl medium. The WOW system resulted in higher blastocyst/oocyte rates for all three modules (single: 59%; group of five: 61%; single zona-digested: 53%) than the culture in drops or in wells (P WOWs per well. The cell number of blastocysts cultured in the WOW system did not differ from that of the controls. Apart from its theoretical value in revealing the role of different factors influencing embryo development in vitro, the WOW system may have immediate practical consequences in certain areas of mammalian embryo production. Copyright 2000 Wiley-Liss, Inc.

A new method for culture of zona-included or zona-free embryos: the Well of the Well (WOW) system

DEFF Research Database (Denmark)

Vajta, Gabor; Peura, T T; Holm, Peter

2000-01-01

(WOW) system. Small wells (WOWs) were formed in four-well dishes by melting the bottom with heated steel rods. The WOWs were then rinsed, the wells were filled with medium, and the embryos were placed into the WOWs. To test the value of the WOW system a 3 x 3 factorial experiment was performed. Bovine......Culture of mammalian zygotes individually and in small groups results in lower developmental rates than culture of large groups. Zona-free zygotes also have impaired developmental potential in current culture systems. This paper describes a new approach to resolve the problems, the Well of the Well...... embryos cultured in 400 microl medium. The WOW system resulted in higher blastocyst/oocyte rates for all three modules (single: 59 group of five: 61 single zona-digested: 53 than the culture in drops or in wells (P well...

Meningite a Herpes zoster num adolescente – uma complicação rara da zona

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Catarina S. Oliveira

2017-06-01

Full Text Available A zona resulta da reativação do vírus varicela-zoster, latente na raíz dorsal dos gânglios sensitivos e nos gânglios dos nervos cranianos, após a resolução da varicela. Existem poucos estudos sobre as complicações da zona na população pediátrica. Enquanto que nos adultos está preconizada terapêutica antivírica específica contra o herpes zoster, nas crianças imunocompetentes o tratamento antivírico é questionável.Os adolescentes encontram-se entre estes dois grupos. O aciclovir é o único antivírico aprovado pela FDA para o tratamento da zona em crianças com menos de dois anos de idade. O valaciclovir, que apresenta uma maior biodisponibilidade, encontra-se aprovado como terapêutica contra a zona nos doentes entre os dois e os 17 anos. Descreve-se o caso de um adolescente, com zona, sem antecedentes patológicos de relevo, que sob terapêutica com aciclovir desenvolveu meningite a herpes-zoster. Questiona-se a abordagem clinica mais correta nos adolescentes imunocompetentes com zona.

LA FRECUENCIA DEL USO DEL USTED EN TRES ZONAS DEL DEPARTAMENTO DE ANTIOQUIA (COLOMBIA

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Ji Son Jang

2014-06-01

Full Text Available En este trabajo se presentan algunos resultados de una investigación sobre la selección pronominal acerca del uso del usted, llevada a cabo en tres municipios del departamento colombiano de Antioquia: la ciudad de Medellín (zona urbana; Carmen de Viboral (zona semirrural, y Andes (zona rural. La población estudiada está constituida por los informantes de edades entre 13 y 34 años. La variable social para este artículo es el lugar de la vivienda de los informantes (zona urbana, semirrural o rural. Para llevar a cabo la investigación, se aplicó un cuestionario, en el cual aparecen distintos tipos interaccionales, a los informantes en las zonas mencionadas; se obtuvieron 1940 informantes. La estadística muestra que, en la gran mayoría de relaciones interpersonales, en Andes se usa más el usted que en Carmen de Viboral y, en este último municipio, más que en Medellín.

LA FRECUENCIA DEL TUTEO EN TRES ZONAS DEL DEPARTAMENTO DE ANTIOQUIA (COLOMBIA: INFLUENCIA DE LA ZONA URBANA/RURAL

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Ji Son Jang

2015-01-01

Full Text Available En este artículo se presentan algunos resultados acerca del uso de tú en el marco de una investigación sobre la selección pronominal llevada a cabo en tres municipios del departamento colombiano de Antioquia: 1 la ciudad de Medellín, capital del departamento; 2 Carmen de Viboral, ubicada a una hora de la capital en automóvil y 3 Andes, que se sitúa a unas tres horas de la capital en coche. Los informantes comprenden edades entre 13 y 34 años. La variable social para este artículo es el lugar de residencia de los informantes: zona urbana (Medellín, medio rural (Carmen de Viboral o rural (Andes. Para llevar a cabo esta investigación se aplicó a 1490 informantes un cuestionario que mostraba distintos tipos de interacción que se dan en dichas zonas. Tres técnicas estadísticas se aplicaron a estos datos: tamaño de muestra óptimo para distribuciones multinomiales; análisis de varianza con un solo factor (ANOVA; y prueba de hipótesis para proporciones. Se encontró que, en la gran mayoría de relaciones interpersonales solidarias, el tuteo se usa más en Medellín que en Carmen de Viboral y en este último municipio más que en Andes.

Análisis de la zona fundida en el crecimiento del compuesto eutéctico Al2O3-ZrO2(Y2O3 por fusión zonal con láser

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Peña, J. I.

2007-10-01

Full Text Available In this work a study of the floating zone during the growth of bars of Al2O3-ZrO2(Y2O3 by the laser floating zone technique is presented. The axial thermal gradient in the solidification interface has been calculated and compared with the experimental one of 6.5*105 K/m. For this calculation the coefficients of heat transference during the solidification process have been determined. The floating zone profile has been also studied and the maximum stable length for the zone determined, verifying the stability criterion established by some authors. The study is completed with an estimation of the laser power necessary to carry out the growth. This value is compared with the measured one during the growth of 2 mm diameter bars.En este trabajo se presenta un estudio de la zona flotante durante el crecimiento de barras de Al2O3-ZrO2 (Y2O3 por la técnica de fusión zonal por láser. Se ha calculado el gradiente térmico axial existente en la intercara de solidificación y comparado con el que se ha medido de forma experimental, siendo éste de 6,5*105 K/m. Para este cálculo se han determinado los coeficientes de transferencia de calor durante el proceso de resolidificación. También se ha estudiado el perfil de la zona flotante y analizado el rango de estabilidad en términos de longitud máxima de zona, verificándose experimentalmente los límites teóricos establecidos por algunos autores. El estudio se completa con una estimación de la potencia necesaria para llevar a cabo el crecimiento confirmando su validez para el caso particular de cilindros de 2 mm de diámetro.

Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin.

Science.gov (United States)

Fasano, A

2000-01-01

The intestinal epithelium represents the largest interface between the external environment and the internal host milieu and constitutes the major barrier through which molecules can either be absorbed or secreted. There is now substantial evidence that tight junctions (tj) play a major role in regulating epithelial permeability by influencing paracellular flow of fluid and solutes. Tj are one of the hallmarks of absorptive and secretory epithelia. Evidence now exists that tj are dynamic rather than static structures and readily adapt to a variety of developmental, physiological, and pathological circumstances. These adaptive mechanisms are still incompletely understood. Activation of PKC either by Zonula occludens toxin (Zot) or by phorbol esters increases paracellular permeability. Alteration of epithelial tj is a recently described property for infectious agents. Clostridium difficile toxin A and B and influenza and vesicular stomatitis viruses have been shown to loosen tj in tissue culture monolayers. Unlike what occurs after the Zot stimulus, these changes appear to be irreversible and are associated with destruction of the tj complex. On the basis of this observation, we postulated that Zot may mimic the effect of a functionally and immunologically related endogenous modulator of epithelial tj. We were able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the zonulins participate in the physiological regulation of intercellular tj not only in the small intestine, but also throughout a wide range of extraintestinal epithelia as well as the ubiquitous vascular endothelium, including the blood-brain barrier. Disregulation of this hypothetical zonulin model may contribute to disease states that involve disordered intercellular communication, including developmental and intestinal disorders, tissue inflammation, malignant transformation, and metastasis.

Zona costeira açoreana tem 7 milhões de anos.

OpenAIRE

Tavares, João

2005-01-01

O director do Departamento de Biologia da Universidade dos Açores, em entrevista ao "Correio dos Açores", refere que as ilhas açorianas tem na zona costeira uma verdadeira fronteira entre o mundo terrestre e o mundo marinho, representando um dos ecossistemas mais ricos do arquipélago. Mas esta zona, com cinco a sete milhões de anos, está mal descrita e incompletamente conhecida, sendo o meio mais transformado por numerosos factores inerentes à presença do Homem. Segundo adianta, o...

Analisis Zona Permeabel Fluida Sistem Panas Bumi Gunungapi Slamet Berdasarkan Analisis Kerapatan Kelurusan Citra SRTM Dan Struktur Geologi

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Sachrul Iswahyudi

2016-03-01

Full Text Available Keberadaan manifestasi panasbumi di sekitar Gunungapi Slamet tidak dapat dipisahkan dari zona-zona permeabilitas yang berkembang. Lokasi-lokasi lulus air tersebut (zona permeabel yang memungkinkan terbentuknya sirkulasi fluida tempat air masuk untuk mengisi reservoir panas bumi dan air keluar ke permukaan bumi sebagai manifesatasi mata air panasbumi di sekitar Gunungapi Slamet. Publikasi yang berupa hasil penelitian ini mencoba mengidentifikasi zona-zona permeabel tersebut berdasarkan anaslisis kerapatan kelurusan yang terekam dalam citra SRTM. Identifikasi kelurusan-kelurusan pada citra berdasarkan komponen-komponen interpretasi citra, yaitu tona, tekstur, pola, bentuk dan relief. Hasil analisis tersebut dikompilasi dengan data struktur geologi regional yang sebelumnya telah diidentifikasi dan data lapangan berupa manifestasi mata air panas. Lokasi-lokasi dengan kerapatan kelurusan yang tinggi pada citra SRTM umumnya bersesuaian dengan zona struktur geologi regional keberadaan manifestasi mata air panas. Daerah tersebut memanjang relatif utara-selatan di bagian barat dan timur-barat di bagian selatan peta. Daerah-daerah inilah yang merupakan daerah lulus air tempat fluida bersirkulasi membentuk sistem panasbumi Gunungapi Slamet.

Zonas de manejo em função de propriedades de solo, relevo e produtividade da lavoura cafeeira

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Bruno Manoel Rezende de Melo

2017-07-01

Full Text Available O objetivo foi determinar zonas de manejo correlacionando produtividade, altitude, parâmetros de textura e fertilidade de solo em propriedades cafeeiras do sul de Minas Gerais. O experimento foi realizado em Inconfidentes (MG, em uma lavoura de café da cultivar Rubi com 0,849 ha-1, no espaçamento 2,2 m x 1,3m, em dezembro de 2011, em Latossolo Vermelho Amarelo distrófico. O local está situado a 957 metros de altitude com parte da lavoura situada no topo de morro e a outra parte em meia encosta, apresentando declividade máxima entre os pontos de maior e menor altitude de 37 %. O local para a coleta de solo está situado em cada ponto georreferenciado com um receptor GPS, para a zona 23k no sistema de referências SIRGAS 2000. Posteriormente foram analisados os parâmetros químicos, físicos, altitude e declividade da área. Para verificar a dependência espacial dos fatores em estudo, utilizou-se da geoestatística. Na presença de dependência espacial foram confeccionados os mapas de gradiente. Os resultados demonstram que não foi possível encontrar dependência espacial para o fósforo. Para as variáveis matéria orgânica, potássio, saturação de bases, pH e declividade, foi possível identificar zonas de manejo em função da correlação significativa com a altitude. A produtividade nos dois anos apresentou variabilidade espacial e temporal. Conclui-se, desta forma, que zonas de manejo podem ser identificadas correlacionando altitude com parâmetros de fertilidade. Para a produtividade e textura nos dois anos de estudos, não foram observadas zonas de manejo.

Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

International Nuclear Information System (INIS)

Kouchi, Zen; Fujiwara, Yuki; Yamaguchi, Hideki; Nakamura, Yoshikazu; Fukami, Kiyoko

2011-01-01

Highlights: → We analyzed Phosphatidylinositol 5-phosphate kinase IIβ (PIPKIIβ) function in cancer. → PIPKIIβ is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. → PIPKIIβ suppresses cellular motility through E-cadherin induction in SW480 cells. → Nuclear PIP 2 but not plasma membrane-localized PIP 2 mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) has anti-cancer activity in several colon cancers. 1α,25(OH) 2 D 3 induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKIIβ) but not PIPKIIα is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLCδ1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLCδ1 PHD inhibited 1α,25(OH) 2 D 3 -induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P 2 production mediates E-cadherin expression through PIPKIIβ in a VDR-dependent manner. PIPKIIβ is also involved in the suppression of the cell motility induced by 1α,25(OH) 2 D 3 . These results indicate that PIPKIIβ-mediated PI(4,5)P 2 signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

Granitoides asociados a zonas de desgarre: modelos analógicos y aplicación al macizo de Lizio (zona de cizalla surarmoricana

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Brun, J. P.

1997-08-01

Full Text Available Granite intrusion in the upper crust along a crustal-scale shear zone has been modeled by injecting a Newtonian fluid (low-viscosity silicone putty into a sandpack containing a ductile layer of silicone putty which acted as a potential décollement level along which the injected material could spread. The strike-slip regime was obtained using a mobile rigid basal plate sliding horizontally. Boundary conditions were chosen in order to analyze the influence of different rheologic profiles of the upper crust on the pattern of the intrusion. Experiments showed that: 1 intrusions are elongate and their long axis tends to track the principal stretching direction associated with the strike-slip regime, 2 intrusions are asymmetric shaped in horizontal view, with the development of a sheared tail trailing behind the intrusion, 3 the strike slip environment allowed local rising of the injected fluid along faults formed in the overburden, 4 when the crustal rheologic profile is similar in both sides of the shear zone, intrusions are asymmetric drop shaped, 5 when the viscosity of materials above the feeding pipe is higher that viscosity of materials of the other side of the shear zone, the asymmetric drop shape not appears. Lizio leucogranite of the South Armorican Shear Zone (South Brittany, France emphasize that our experiments can explain the geometry of many syntectonic' granites emplaced along strike-slip zones. They further shed some light on mechanisms of pluton intrusion in the upper crust.El emplazamiento de granitoides en zonas de desgarre de la corteza superior se ha modelizado inyectando un fluido newtoniano en un paquete de arena en el cual se intercala una capa dúctil de silicona que actúa como un nivel de despegue potencial en el cual el material inyectado puede expandirse. El régimen de desgarre se obtiene utilizando una placa basal rígida y móvil que desliza horizontalmente. Se ha analizado la influencia de diferentes perfiles reol

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

Science.gov (United States)

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Lipofection of siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well culture system.

Science.gov (United States)

Ikeda, Shuntaro; Sugimoto, Miki; Kume, Shinichi

2018-04-13

Bovine preimplantation embryos exhibit dramatic biological changes between before and after the 8-16-cell stage. Here we report a simple lipofection method to transfect siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well (WOW) culture system. Bovine one-cell embryos produced in vitro were freed from the zona pellucida and cultured up to the 8-16-cell stage in WOW dishes. The 8-16-cell embryos were lipofected with siRNA and the transfection efficiency was assessed at 48 h of transfection. Lipofection with a red fluorescent non-targeting siRNA revealed the importance of zona removal for transfection of siRNA into embryos. Using this method, we knocked down the methionine adenosyltransferase 2A (MAT2A) gene, achieving a significant reduction in MAT2A expression (P lipofection', may be useful to analyze gene functions in bovine preimplantation embryos without expensive equipment and skill-intensive techniques.

Detection of cholera (ctx) and zonula occludens (zot) toxin genes in Vibrio cholerae O1, O139 and non-O1 strains.

Science.gov (United States)

Rivera, I G; Chowdhury, M A; Sanchez, P S; Sato, M I; Huq, A; Colwell, R R; Martins, M T

1995-09-01

Vibrio cholerae O1 and V. cholerae non-O1 strains isolated from environmental samples collected in São Paulo, Brazil, during cholera epidemics and pre-epidemic periods were examined for the presence of toxin genes. V. cholerae O1 strains isolated from clinical samples in Peru and Mexico, and V. cholerae O139 strains from India were also examined for the presence of ctx (cholera toxin gene) and zot (zonula occludens toxin gene) by polymerase chain reaction (PCR). A modified DNA-extraction method applied in this study yielded satisfactory recovery of genomic DNA from vibrios. Results showed that strains of V. cholerae O1 isolated during the preepidemic period were ctx (-)/zot (-) whereas strains isolated during the epidemic were ctx (+)/zot (+). All V. cholerae non-O1 strains tested in the study were ctx (-)/zot (-), whereas all V. cholerae O139 strains were ctx (+)/zot (+). Rapid detection of the virulence genes (ctx and zot) can be achieved by PCR and this can serve as an important tool in the epidemiology and surveillance of V. cholerae.

Dinâmica Glacial e Características Sedimentares Resultantes na Zona Proglacial da Geleira Ecology-Baía do Almirantado, Ilha Rei George Antártica.

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Kátia Kellem Rosa

2006-12-01

Full Text Available A geleira Ecology, localizada na ilha Rei George, ilhas Shetlands do Sul, está sofrendo um processo de rápida retração ao longo das últimas décadas, sendo que no período de 1956 a 1992/95 a geleira retrocedeu 0,37 Km2. Isto gerou um ambiente de deglaciação, com a exposição de várias geoformas na zona proglacial. Este trabalho objetiva estudar o ambiente de deglaciação da zona proglacial da geleira Ecology e seus respectivos depósitos na zona proglacial, além de inferir o regime termo-basal desta geleira. O produto resultante deste trabalho é a criação de um modelo geomorfológico para a zona proglacial da geleira, o qual pode ser usado para comparar com zonas proglaciais de outras geleiras.

INVENTARISASI JENIS ARTHROPODA DAN ECHINODERMATA DI ZONA PASANG SURUT TIPE SUBSTRAT BERBATU PANTAI GATRA KABUPATEN MALANG

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Arindra Trisna Widiansyah

2016-07-01

Pantai Gatra merupakan salah satu ekowisata pantai di Kabupaten Malang yang memiliki zona pasang surut dengan substrat dominan batu. Substrat berbatu merupakan daerah yang paling padat makroorganismenya. Arthropoda dan Echinodermata mempunyai peranan penting dari segi sumber makanan maupun ekologi. Mengingat belum adanya pelaporan jenis Arthropoda dan Echinodermata di zona pasang surut Pantai Gatra, maka dilakukan penelitian inventarisasi di daerah ini. Tujuan penelitian ini adalah invetarisasi jenis Arthropoda dan Echinodermata. Hasil penelitian tentang inventarisasi jenis Arthropoda dan Echinodermata di zona pasang surut pantai Gatra Kabupaten Malang, secara keseluruhan ditemukan 14 jenis, 13 genus, dan 11 famili dari filum Arthropoda dan Echinodermata.

Effect of zona pellucida on porcine parthenogenetically activated embryos

DEFF Research Database (Denmark)

Li, Rong; Liu, Ying; Li, Juan

2011-01-01

μg mL–1 cytochalasin B and 10 μg mL–1 cycloheximide in PZM-3 medium for 4 h. ZP was removed by 3.3 mg mL–1 pronase. Both zona-intact (PAZI) and zona-free (PAZF) embryos were cultured individually for 6 days either in time-lapse incubator (Embryoscope D, Unisense A/S, Aarhus, Denmark) for 15-min......). The timing of morulae was recorded when they completed compaction. Good blastocysts were defined when they expanded to 1.5 times larger than oocytes and formed regular blastocoel cavity with uniform colour and distribution of cells. Timing data were analysed by Student's t-test, while development rates....... 22, 234). In the present study, we expanded this study to include also the timing of early development and the resulting quality and robustness (for vitrification) of porcine PA embryos. Parthenogenetic activation was made first by an electric pulse (1.26 kV cm–1, 80 μs) and then by incubation with 5...

La crisis de deuda soberana de los PIGS de la zona euro

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Jourdy V. James Heredia

2014-01-01

Full Text Available Portugal, Irlanda, Grecia y España, nombrados por sus iniciales los PIGS de la zona euro, desde el 2010 hasta la actualidad han reflejado desequilibrios fiscales considerables y niveles de endeudamiento que se han hecho inmanejables. A la vez que padecen profundas crisis en sus sistemas bancarios, pobres tasas de crecimiento económico y altos niveles de de desempleo. Ante esta situación la investigación analiza las diferentes políticas económicas (monetaria, fiscal, así como el tipo de cambio en la zona euro y se llega a la conclusión que la salida de la actual situación de crisis de los PIGS depende del logro de un crecimiento económico sostenido. Sobre esta base, la solución al problema económico de los PIGS parecer ser política y, a corto plazo incluye: la necesidad de una cooperación mayor dentro de la eurozona así como cambios en la política económica seguida hasta el momento y en la principal institución monetaria de la zona, entre otros elementos.

Evidence that the EphA2 receptor exacerbates ischemic brain injury.

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John Thundyil

Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

Expression patterns of tight junction components induced by CD24 in an oral epithelial cell-culture model correlated to affected periodontal tissues.

Science.gov (United States)

Ye, P; Yu, H; Simonian, M; Hunter, N

2014-04-01

Previously we demonstrated uniformly strong expression of CD24 in the epithelial attachment to the tooth and in the migrating epithelium of the periodontitis lesion. Titers of serum antibodies autoreactive with CD24 peptide correlated with reduced severity of periodontal disease. Ligation of CD24 expressed by oral epithelial cells induced formation of tight junctions that limited paracellular diffusion. In this study, we aimed to reveal that the lack of uniform expression of tight junction components in the pocket epithelium of periodontitis lesions is likely to contribute to increased paracellular permeability to bacterial products. This is proposed as a potential driver of the immunopathology of periodontitis. An epithelial culture model with close correspondence for expression patterns for tight junction components in periodontal epithelia was used. Immunohistochemical staining and confocal laser scanning microscopy were used to analyse patterns of expression of gingival epithelial tight junction components. The minimally inflamed gingival attachment was characterized by uniformly strong staining at cell contacts for the tight junction components zona occludens-1, zona occludens-2, occludin, junction adhesion molecule-A, claudin-4 and claudin-15. In contrast, the pocket epithelium of the periodontal lesion showed scattered, uneven staining for these components. This pattern correlated closely with that of unstimulated oral epithelial cells in culture. Following ligation of CD24 expressed by these cells, the pattern of tight junction component expression of the minimally inflamed gingival attachment developed rapidly. There was evidence for non-uniform and focal expression only of tight junction components in the pocket epithelium. In the cell-culture model, ligation of CD24 induced a tight junction expression profile equivalent to that observed for the minimally inflamed gingival attachment. Ligation of CD24 expressed by gingival epithelial cells by lectin

Involvement of adenosine monophosphate activated kinase in interleukin-6 regulation of steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme in the bovine zona fasciculata and zona reticularis.

Science.gov (United States)

De Silva, Matharage S I; Dayton, Adam W; Rhoten, Lance R; Mallett, John W; Reese, Jared C; Squires, Mathieu D; Dalley, Andrew P; Porter, James P; Judd, Allan M

2018-06-01

In bovine adrenal zona fasciculata (ZF) and NCI-H295R cells, interleukin-6 (IL-6) increases cortisol release, increases expression of steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) (increases steroidogenic proteins), and decreases the expression of adrenal hypoplasia congenita-like protein (DAX-1) (inhibits steroidogenic proteins). In contrast, IL-6 decreases bovine adrenal zona reticularis (ZR) androgen release, StAR, P450scc, and SF-1 expression, and increases DAX-1 expression. Adenosine monophosphate (AMP) activated kinase (AMPK) regulates steroidogenesis, but its role in IL-6 regulation of adrenal steroidogenesis is unknown. In the present study, an AMPK activator (AICAR) increased (P < 0.01) NCI-H295R StAR promoter activity, StAR and P450scc expression, and the phosphorylation of AMPK (PAMPK) and acetyl-CoA carboxylase (PACC) (indexes of AMPK activity). In ZR (decreased StAR, P450scc, SF-1, increased DAX-1) (P < 0.01) and ZF tissues (increased StAR, P450scc, SF-1, decreased DAX-1) (P < 0.01), AICAR modified StAR, P450scc, SF-1 and DAX-1 mRNAs/proteins similar to the effects of IL-6. The activity (increased PAMPK and PACC) (P < 0.01) of AMPK in the ZF and ZR was increased by AICAR and IL-6. In support of an AMPK role in IL-6 ZF and ZR effects, the AMPK inhibitor compound C blocked (P < 0.01) the effects of IL-6 on the expression of StAR, P450scc, SF-1, and DAX-1. Therefore, IL-6 modification of the expression of StAR and P450scc in the ZF and ZR may involve activation of AMPK and these changes may be related to changes in the expression of SF-1 and DAX-1. Copyright © 2018 Elsevier Inc. All rights reserved.

Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain.

Science.gov (United States)

Di Pierro, M; Lu, R; Uzzau, S; Wang, W; Margaretten, K; Pazzani, C; Maimone, F; Fasano, A

2001-06-01

Zonula occludens toxin (Zot) is an enterotoxin elaborated by Vibrio cholerae that increases intestinal permeability by interacting with a mammalian cell receptor with subsequent activation of intracellular signaling leading to the disassembly of the intercellular tight junctions. Zot localizes in the bacterial outer membrane of V. cholerae with subsequent cleavage and secretion of a carboxyl-terminal fragment in the host intestinal milieu. To identify the Zot domain(s) directly involved in the protein permeating effect, several zot gene deletion mutants were constructed and tested for their biological activity in the Ussing chamber assay and their ability to bind to the target receptor on intestinal epithelial cell cultures. The Zot biologically active domain was localized toward the carboxyl terminus of the protein and coincided with the predicted cleavage product generated by V. cholerae. This domain shared a putative receptor-binding motif with zonulin, the Zot mammalian analogue involved in tight junction modulation. Amino acid comparison between the Zot active fragment and zonulin, combined with site-directed mutagenesis experiments, confirmed the presence of an octapeptide receptor-binding domain toward the amino terminus of the processed Zot.

Influencia de los contaminantes SO2 y NO2 en la formación de lluvia ácida en la zona metropolitana de Guadalajara, Jalisco, México

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Mario E. García G.

2006-01-01

Full Text Available La Zona Metropolitana de Guadalajara (ZMG a raíz de un intenso desarrollo urbano e industrial desde la segunda mitad del siglo XX, ha presentado problemas de contaminación ambiental y, en particular, la presencia de lluvias ácidas. En este trabajo, por primera vez, se realizó un estudio para determinar la concentración de contaminantes depositados por agua de lluvia y para tal efecto, se implementó una red pluviométrica con 17 estaciones distribuidas en la ZMG. Se analizaron las temporadas de lluvias durante el período 1994-2002 en el intervalo de junio a septiembre. Los compuestos analizados fueron, potencial hidrógeno (pH, sulfatos (SO4 2-, nitratos (NO3 - y cloruros (Cl-. Para evaluar la influencia del bióxido de azufre (SO2 y bióxido de nitrógeno (NO2 (principales precursores de la lluvia ácida, se utilizó la información del banco de datos de las 8 estaciones de la Red Automática de Monitoreo Atmosférico (RAMA proporcionados por la Secretaria del Medio Ambiente para el Desarrollo Sustentable de Jalisco (SEMADES. Los resultados de este trabajo mostraron que la contaminación atmosférica ha modificado la naturaleza química de la lluvia, con tendencia a incrementar su concentración ácida. Las concentraciones más elevadas de SO2 y NO2 en el aire correspondieron a 1999, las cuales fueron también máximas para el SO4 2- y NO3 - en la lluvia. En contraparte, en la temporada de lluvia del 2002 se encontraron concentraciones máximas de Cl- coincidiendo con el desarrollo de la industria plástica en la zona. Las condiciones dinámicas atmosféricas favorecieron la tendencia ácida dominante hacia el oeste de la ZMG

HUBUNGAN KECEPATAN RELATIF PERGERAKAN LEMPENG DENGAN TINGKAT SEISMISITAS DI ZONA SUBDUKSI

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Muzli Muzli

2015-04-01

Full Text Available Perbedaan tingkat aktifitas gempabumi tektonik di zona subduksi dapat disebabkan oleh banyak faktor. Salah satu faktornya diduga akibat adanya pengaruh dari kecepatan relatif pergerakan lempeng. Studi terhadap hubungan antara kecepatan gerak lempeng dengan seismisitas dilakukan dengan menggunakan data gempabumi dan kecepatan relatif pergerakan lempeng pada beberapa zona subduksi di dunia. Jumlah data gempabumi diplot sebagai fungsi dari kecepatan relatif pergerakan lempeng. Hasil studi ini menunjukkan bahwa tingkat seismisitas gempabumi di zona subduksi dipengaruhi oleh kecepatan relatif pergerakan lempeng. Kedua parameter menunjukkan hubungan linear yang sangat baik dengan koefisien korelasi 0,98. Secara fisis hal ini menegaskan bahwa hukum kekekalan energi berlaku pada proses pergerakan lempeng di zona subduksi, dimana energi gerak lempeng berubah ke dalam bentuk pelepasan energi berupa gempabumi. Hasil studi ini juga menunjukkan bahwa jumlah gempabumi dengan magnitudo lebih besar dari 4 dan kedalaman lebih kecil dari 60 km dapat dihitung secara teoritis dengan menggunakan rumusan empiris.   Subduction zones are seismically the most active areas around the world. However, the seismicity rate among subduction zones is different. This can be caused by many reasons. One of them expected to be influenced by the relative plate velocity. Analysis of correlation between relative plate velocities and seismicity rate around subduction zones in the world has been done in this study. The correlation was analysed by plotting number of earthquake events as function of relative plate velocities. The results show that the seismicity rate is linearly influenced by relative plate velocities with the correlation coefficient of 0,98. Physically it is asserted that the law of conservation of energy applies to the movement of the plates in subduction zones, where plate motion changed to energy in the form of energy release of earthquakes. The results of this

Levantamiento topográfico zona calle Pedro Martín Zermeño

OpenAIRE

Vizcaíno Cortés, Gloria

2015-01-01

El objetivo de dicho proyecto es la realización de un levantamiento topográfico de dicha zona de la ciudad de Cartagena y el correspondiente plano topográfico, parte de la necesidad de actualizar un plano realizado por la Comunidad Autónoma de Murcia ya que el actual se encuentra obsoleto. Mediante este proyecto fin de carrera se pretende llevar a cabo la realización de un plano a escala 1/500 de la zona. Haremos una modernización de la cartografía además de incluir los cambios realizados por...

Trastornos Asociados a la Deficiencia de Yodo. Vigilancia permanente es deficitaria en zonas vulnerables

OpenAIRE

Hernando Vargas-Uricoechea; Carlos Hernán Sierra-Torres; Claudia Milena Holguín Betancourt; Laura Cristancho Torres

2012-01-01

Los Desórdenes por Deficiencia de Yodo (DDY) son uno de los mayores problemas en salud pública en el mundo actual, en especial en niños y embarazadas. Estos trastornos truncan el desarrollo socioeconómico en aquellas zonas que los padecen; las poblaciones que viven en zonas yodo-deficientes siempre van a estar expuestas a sufrir las consecuencias originadas por esta deficiencia, en especial el aumento en la mortalidad perinatal, retardo mental, alteraciones en la síntesis de hormonas tiroide...

Análise Espacial da Produtividade de Óleo Vegetal para Produção de Biodiesel na Zona da Mata Mineira

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Rudolph Fabiano Alves Pedroza Teixeira

2008-01-01

Full Text Available Since the late 1990’s vegetable oils have been conquering an increasing importance in the world.In virtue of reducing the CO2 emissions and promoting regional development, the biodieselemerges as a viable alternative. Hence this articleappraises the productivity of vegetable oil forthe production of biodiesel in the Zona da Mata Mineira over the period 2005/2006, using theexploratory spatial data analysis. In order to measure the productive potential of vegetable oil atthe regional level, one calculates the content of oil for each vegetable and these contents aresummed up to obtain the total of vegetable oil. Clusters were identified for the production ofvegetables both the high efficiency and low efficiency. The finding reveal the possibility ofgenerating jobs in most regions within Zona da MataMineira. Hence one observes the plantation ofvegetables for the production of biodiesel is highly viable in the Zona da Mata Mineira

Modelagem da retenção de herbicidas em zonas ripárias Modeling of herbicide retention in riparian zones

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Alexandra P. de Pinho

2006-12-01

Full Text Available O presente trabalho teve como objetivo investigar a retenção de atrazina e picloram, transportados via escoamento superficial, em zona ripária. Para isto, simulou-se um escoamento superficial, contendo uma mistura de caulinita, atrazina e picloram, dentro de zonas ripárias estabelecidas ao longo de plantações de pinheiros do Nordeste do Estado da Geórgia, EUA. Cinco parcelas foram instaladas dentro de zonas ripárias, apresentando declividades diferentes (2, 5, 10, 15 e 20%. Os efeitos da umidade do solo e da presença do horizonte O na retenção dos dois herbicidas foram avaliados. Um modelo exponencial, comumente utilizado na estimativa de redução da DBO e de nutrientes em tratamento por escoamento superficial, foi empregado na estimativa de redução de herbicidas e caulinita em zonas ripárias. O modelo possibilitou estimar com razoável precisão, a remoção de caulinita e atrazina da mistura em escoamento ao longo de zonas ripárias de 10 m de comprimento. Em geral, a declividade foi o parâmetro que apresentou melhor correlação com a retenção dos contaminantes presentes na mistura em escoamento na zona ripária. O horizonte O, mais espesso nas maiores declividades, favoreceu tanto a sedimentação da caulinita como a adsorção da atrazina.This work aimed to investigate the retention of atrazine and picloram, carried by surface flow, in riparian zones. The surface flow, containing a mixture of both herbicides and kaolin, was then simulated within riparian zones established in pine plantations in north-eastern Georgia, USA. Five plots were established within riparian zones, each with a different slope (2, 5, 10, 15 and 20%. The influence of the initial moisture and of the O horizon condition in herbicide retention was analyzed. An exponential model, commonly used for the estimate of biochemical demand of oxygen (BOD and nutrients attenuation in overland flow treatment, was used to estimate the attenuation of kaolin and

Determinación de zonas expuestas a la ocurrencia de accidentes por transporte de mercancías peligrosas en Colombia

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Cristian Camilo Fernández Lopera

2015-06-01

Full Text Available La gestión del riesgo debe ser un componente transversal del desarrollo de la sociedad y de acuerdo con la Ley 1523 de 2012 en Colombia, debe involucrar a entidades gubernamentales, sociedad civil y sector privado, trascendiendo los límites territoriales. El objetivo de esta investigación fue determinar zonas expuestas a la ocurrencia de accidentes que involucran transporte de mercancías peligrosas en los municipios de Dosquebradas, Pereira y La Virginia, que conforman el Área Metropolitana Centro Occidente en Colombia. Las mercancías peligrosas fueron identificadas mediante el reconocimiento de las principales actividades industriales del área de estudio y se analizaron los corredores viales por los cuales ellas son transportadas, determinando zonas de alta accidentalidad. Se realizó una simulación de dispersión de sustancias mediante el aplicativo WISER y se identificaron zonas de riesgo en cada municipio. Los resultados indicaron que las zonas de mayor exposición a accidentes con mercancías peligrosas son: vía Pereira-LaVirginia; sector Cerritos-La Villa (Pereira; sector de Playa Rica; rotonda de Postobón; la zona entre la rotonda de Postobón y la rotonda de Makro (Dosquebradas; y rotonda de calle 12B con la carrera 7a (La Virginia. En todos los corredores viales por los cuales se transportan mercancías peligrosas existen zonas críticas de alta accidentalidad.

The Pattern of Tyrosine Phosphorylation in Human Sperm in Response to Binding to Zona Pellucida or Hyaluronic Acid

Science.gov (United States)

Sati, Leyla; Cayli, Sevil; Delpiano, Elena; Sakkas, Denny

2014-01-01

In mammalian species, acquisition of sperm fertilization competence is dependent on the phenomenon of sperm capacitation. One of the key elements of capacitation is protein tyrosine phosphorylation (TP) in various sperm membrane regions. In previous studies performed, the pattern of TP was examined in human sperm bound to zona pellucida of oocytes. In the present comparative study, TP patterns upon sperm binding to the zona pellucida or hyaluronic acid (HA) were investigated in spermatozoa arising from the same semen samples. Tyrosine phosphorylation, visualized by immunofluorescence, was localized within the acrosomal cap, equatorial head region, neck, and the principal piece. Tyrosine phosphorylation has increased in a time-related manner as capacitation progressed, and the phosphorylation pattern was identical within the principal piece and neck, regardless of the sperm bound to the zona pellucida or HA. Thus, the data demonstrated that the patterns of sperm activation-related TP were similar regardless of the spermatozoa bound to zona pellucida or HA. Further, sperm with incomplete development, as detected by excess cytoplasmic retention, failed to exhibit TP. PMID:24077441

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying-Nan P.; LaMarche, Matthew J.; Chan, Ho Man; Fekkes, Peter; Garcia-Fortanet, Jorge; Acker, Michael G.; Antonakos, Brandon; Chen, Christine Hiu-Tung; Chen, Zhouliang; Cooke, Vesselina G.; Dobson, Jason R.; Deng, Zhan; Fei, Feng; Firestone, Brant; Fodor, Michelle; Fridrich, Cary; Gao, Hui; Grunenfelder, Denise; Hao, Huai-Xiang; Jacob, Jaison; Ho, Samuel; Hsiao, Kathy; Kang, Zhao B.; Karki, Rajesh; Kato, Mitsunori; Larrow, Jay; La Bonte, Laura R.; Lenoir, Francois; Liu, Gang; Liu, Shumei; Majumdar, Dyuti; Meyer, Matthew J.; Palermo, Mark; Perez, Lawrence; Pu, Minying; Price, Edmund; Quinn, Christopher; Shakya, Subarna; Shultz, Michael D.; Slisz, Joanna; Venkatesan, Kavitha; Wang, Ping; Warmuth, Markus; Williams, Sarah; Yang, Guizhi; Yuan, Jing; Zhang, Ji-Hu; Zhu, Ping; Ramsey, Timothy; Keen, Nicholas J.; Sellers, William R.; Stams, Travis; Fortin , Pascal D. (Novartis)

2016-06-29

The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase1. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma1, 2, 3, 4, 5. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway2, 3. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways6, 7. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy8, 9. Here we report the discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

Sistemas de Producción Campesina en la Zona de Colonización del Departamento del Guaviare

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Vélez Vargas León Darío

1994-09-01

Full Text Available De acuerdo con los objetivos de este Panel sobre las formas de producción agrícola en Colombia, la primera parte de esta ponencia describirá y evaluará los sistemas de producción campesinos en unos de los frentes de colonización más activos en la Amazonía colombiana, el Departamento del Guaviare. Luego de ubicar geográfica, histórica, biofísica y socio-económicamente la zona de estudio y también respecto a los usos del suelo, la ponencia centrará sus análisis en los sistemas de producción que se presentan en las zonas de influencia de los ríos Guaviare y Guayabera (Terrazas y Vegas. El estudio de los sistemas de producción en la zona referida, se inicia con la descripción analítica de la apropiación del medio natural por parte del colono. A continuación se describen y analizan los principales usos del suelo particularizando el uso agrícola, en donde se estudian los cultivos, los arreglos productivos y sus principales limitantes. Después de estudiar los sistemas de producción a nivel de zona, se estudian a nivel de unidad de producción, analizando la racionalidad y estrategias que adopta el colono para su manejo. En la segunda parte la ponencia, se discute el rol de los profesionales agrarios y de los centros de educación superior en estos sistemas de producci6n y en las zonas de colonización y se concluye que los primeros no están capacitados para afrontar, de manera adecuada, las necesidades y posibilidades de estos sistemas y de estas zonas, ya que los centros donde se han formado, no suministran los elementos necesarios para ello, a pesar de que históricamente la frontera agrícola de Colombia ha crecido gracias al proceso permanente de colonización.

Un indice de peligrosidad para zonas laterales de carreteras de dos carriles

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Juan Ignacio Rivera

2014-01-01

Full Text Available Las zonas laterales de carreteras son elementos destinados a reducir la severidad de accidentes por salida de calzada. La peligrosidad es un indicador de cumplimiento de este objetivo. Existen pocos métodos para medir peligrosidad, que usualmente dependen de la disponibilidad de datos de accidentes. Este trabajo estudia los factores que explican la peligrosidad con base en modelos existentes y el análisis de datos de campo. Se determinó que el despeje lateral junto a las barreras de protección, especialmente en curvas con taludes inclinados, es significativo para explicar la peligrosidad. Se determinó que en rectas y curvas sin barreras de protección es relevante el tipo de objeto y su posición en la zona lateral.

Zonas y métodos de entrenamiento de la resistencia cardiorrespiratoria

OpenAIRE

García Pallarés, Jesús

2015-01-01

Propuesta metodológica para el desarrollo de los ritmos y zonas de entrenamiento de la resistencia en función de la posición de los hitos fisiológicos de la vía aeróbica y sus factores limitantes.

Hidrología de la zona vadosa en la terraza de Llanogrande (Rionegro – Antioquia)

OpenAIRE

Tobón, Jorge Iván

2003-01-01

La zona de Llanogrande es una región fundamental en el desarrollo de Antioquia y es la de más rápido crecimiento poblacional, comercial e industrial del Departamento. Esto hace que se demande grandes cantidades de agua, siendo la subterránea una de las principales fuentes actuales y hacia el futuro. Con este trabajo se pretende aportar al conocimiento de la dinámica del agua en la zona vadosa de la Terraza de Llanogrande (Rionegro – Antioquia), a partir de las propiedades físicas e hidrául...

Cloned cattle derived from a novel zona-free embryo reconstruction system

NARCIS (Netherlands)

Oback, B; Wiersema, AT; Gaynor, P; Laible, G; Tucker, FC; Oliver, JE; Miller, AL; Troskie, HE; Wilson, KL; Forsyth, JT; Berg, MC; Cockrem, K; Mcmillan, [No Value; Tervit, HR; Wells, DN

2003-01-01

As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production

“Tomar” e “Zona Monumental de Ajuda Belem”. Dois projectos de salvaguardia, dois casos de estudo

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Isabel Maria Augusto de Sousa Rosa

2008-12-01

Full Text Available Prosseguindo os propósitos deste Il Seminário internacional “Conservazione del Património Arquitectónico e Urbano”, onde irão ser confrontadas as experiências realizadas em Itália e Portugal no âmbito da conservação do património arquitectónico e urbano, são apresentados dois casos de estudo, objectivando a salvaguarda dos centros históricos, realizados em duas cidades portuguesas - Tomar (Centro Histórico e Lisboa (Zona Monumental Ajuda-Belém. Os dois Planos então realizados – Tomar, em 1996, e zona monumental Ajuda-Belém, em 2004 – ambos recorrendo a suporte informático, evidenciam na “decalage” de 8 anos, a importância dos avanços tecnológicos e informáticos, patente no projecto mais recente (Zona Monumental Ajuda - Belém, quer na aquisição e processamento de dados, quer ainda na consulta dos mesmos, processos que se têm revelado valiosíssimos para a conservação e salvaguarda do património arquitectónico, urbano e ambiental desta zona da cidade de Lisboa.

Estudio preliminar de la creación de una “zona caliente” en YBa2Cu3O7-δ utilizando una corriente continua

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Evetts, J. E.

1999-12-01

Full Text Available This work presents a study of the processes that give rise to the Direct Current Zoning effect. This effect consists in the formation of a hot zone in a superconducting rod when a potential difference is applied to it. The superconducting material used in this case was YBa2Cu3O7-δ. The formation and movement of the zone in the bar can be explained studying the balance between the ionic fluxes created due to the potential difference and to the temperature distribution along the bar. This paper presents the theoretical results obtained using a computer model developed that takes into account the processes of electromigration and ionic diffusion that give rise to the Direct Current Zoning effect.Este trabajo presenta un estudio de los procesos que dan lugar al fenómeno en el que un “punto” o zona caliente se forma al aplicar una diferencia de potencial a los extremos de una barra de óxido superconductor. El material superconductor utilizado en este caso es YBa2Cu3O7-δ. El equilibrio entre los flujos iónicos debidos a la diferencia de potencial y a la distribución de temperatura se han utilizado para explicar la formación y el movimiento de la zona a lo largo de la muestra. Este artículo presenta los resultados teóricos obtenidos utilizando un modelo que tiene en cuenta los procesos de electromigración y difusión iónica que dan lugar a este fenómeno.

Photosynthesis-Inhibiting Activity of 1-[(2-Chlorophenylcarbamoyl]- and 1-[(2-Nitrophenylcarbamoyl]naphthalen-2-yl Alkylcarbamates

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Tomas Gonec

2017-07-01

Full Text Available Eight 1-[(2-chlorophenylcarbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenylcarbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC50 values ranged from 0.05 to 0.664 mmol/L; and the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl-carbamoyl]naphthalen-2-yl propylcarbamate. It has been proven that the compounds are PET-inhibitors in photosystem II. Despite rather low PET-inhibiting activities, primary structure-activity trends can be discussed.

Pérdidas de suelo y nutrientes bajo diferentes coberturas vegetales en la zona Andina de Colombia

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Rodríguez José Alexander

2009-09-01

Full Text Available El estudio se realizó en la reserva natural El Ciprés, ubicada en la vereda Bellavista, municipio de El Dovio (Valle del Cauca. La vereda se encuentra en la zona Andina de la cordillera occidental, en el departamento del Valle del Cauca, entre 1700 y 1800 m.s.n.m., con una temperatura promedio de 18 °C. Según la clasificación climática de Holdridge, corresponde a una zona de bosque húmedo Montano Bajo, con una precipitación promedio entre 2500 y 2700 mm/año, una humedad relativa de 90% y una pendiente del suelo de 62%. Las mediciones se hicieron en parcelas de escorrentía de 32 m2 cada una y siete tipos de coberturas: guadua (Guadua angustifolia Kunth, bosque secundario, pastura (Brachiaria decumbens, café (Coffea arabica; banco de proteína (Trichanthera gigantea, caña forrajera (Saccharum officinarum y cultivo limpio conformado por yuca (Manihot esculenta, maíz (Zea mays y arracacha (Arracacia zanthorrhiza Brancroft. Para la evaluación se midieron las pérdidas de suelo y los nutrientes calcio, magnesio, potasio y fósforo en un periodo de 7 meses. Los resultados mostraron diferencias (P < 0.05 entre las coberturas evaluadas. Las pérdidas más altas de suelo y nutrientes ocurrieron bajo cultivos limpios (2.61 t/ha y las más bajas en guadua (0.08 t/ha. Estos resultados sugieren ventajas de los bosques de guadua en esta zona de Colombia, ya que además de contribuir a la conservación de los suelos y al mantenimiento de la fertilidad, es una alternativa económica complementaria para los productores rurales a partir de su manejo y aprovechamiento.

Cysteine-independent activation/inhibition of heme oxygenase-2

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Dragic Vukomanovic

2016-01-01

Full Text Available Reactive thiols of cysteine (cys residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2 isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2 and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

Cysteine-independent activation/inhibition of heme oxygenase-2.

Science.gov (United States)

Vukomanovic, Dragic; Rahman, Mona N; Maines, Mahin D; Ozolinš, Terence Rs; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

2016-03-01

Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins.

Science.gov (United States)

Hanas, J S; Rodgers, J S; Bantle, J A; Cheng, Y G

1999-11-01

The association of lead with chromatin in cells suggests that deleterious metal effects may in part be mediated through alterations in gene function. To elucidate if and how lead may alter DNA binding of cysteine-rich zinc finger proteins, lead ions were analyzed for their ability to alter the DNA binding mechanism of the Cys(2)His(2) zinc finger protein transcription factor IIIA (TFIIIA). As assayed by DNase I protection, the interaction of TFIIIA with the 50-bp internal control region of the 5S ribosomal gene was partially inhibited by 5 microM lead ions and completely inhibited by 10 to 20 microM lead ions. Preincubation of free TFIIIA with lead resulted in DNA-binding inhibition, whereas preincubation of a TFIIIA/5S RNA complex with lead did not result in DNA-binding inhibition. Because 5S RNA binds TFIIIA zinc fingers, this result is consistent with an inhibition mechanism via lead binding to zinc fingers. The complete loss of DNase I protection on the 5S gene indicates the mechanism of inhibition minimally involves the N-terminal fingers of TFIIIA. Inhibition was not readily reversible and occurred in the presence of an excess of beta-mercaptoethanol. Inhibition kinetics were fast, progressing to completion in approximately 5 min. Millimolar concentrations of sulfhydryl-specific arsenic ions were not inhibitory for TFIIIA binding. Micromolar concentrations of lead inhibited DNA binding by Sp1, another Cys(2)His(2) finger protein, but not by the nonfinger protein AP2. Inhibition of Cys(2)His(2) zinc finger transcription factors by lead ions at concentrations near those known to have deleterious physiological effects points to new molecular mechanisms for lead toxicity in promoting disease.

Inhibition of hepatic lipogenesis by 2-tetradecylglycidic acid.

Science.gov (United States)

McCune, S A; Nomura, T; Harris, R A

1979-10-01

2-Tetradecylglycidic acid (TDGA), a hypoglycemic agent, has been found to be a very effective inhibitor of de novo fatty acid synthesis by isolated hepatocytes. A comparison was made between the effectiveness of TDGA and 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, on the metabolic processes of isolated hepatocytes. These compounds are structurally related and both inhibit fatty acid synthesis; however, they have opposite effects from each other on the oxidation and esterification of fatty acids. TDGA inhibits whereas TOFA stimulates fatty acid oxidation. TDGA stimulates whereas TOFA inhibits fatty acid esterification.

ALTERNATIVA DE CORREDOR ECOLÓGICO EN LA ZONA NORORIENTAL DEL MUNICIPIO DE MEDELLÍN

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VILLA GRAJALES ANA MARÍA

2012-11-01

Full Text Available El presente trabajo se realizó con el objetivo de establecer una alternativa de corredor ecológico de conexión estructural en las comunas 1, 2, 3 y 4 de la zona nor-oriental del municipio de Medellín, orientada a la  protección del suelo verde existente y a la toma de decisiones en cuanto a la generación de nuevo suelo, utilizando las métricas del paisaje y herramientas geoinformaticas. Se utilizó un área de 400 m² como Unidad Mínima Cartografiable (UMC, encontrándose 296 ha (19,4% de áreas verdes respecto a las 1.527 ha de área de estudio, predominando la cobertura de pasto con 95,4 ha, mientras que la zona arbolada, con un área de 26,1 ha, mostró el mayor aislamiento (99,1 m, y el rastrojo alto con 48,7 ha presentó la mayor agregación (16,4 m. Se priorizaron ocho (8 fragmentos para la conservación, seleccionados a través del Índice de Calidad del Fragmento (ICF, sumando en total 26 ha. El corredor se estableció con un ancho de 80 m, arrojando un área total de 73,2 ha, asociada, en su mayoría, a retiros de quebradas.

Levantamiento topográfico zona El Batel (Cartagena)

OpenAIRE

Pérez Lozano, David

2015-01-01

El objetivo del proyecto es el levantamiento topográfico tanto del Auditorio El Batel como de la carretera, rotonda y césped justo debajo de la muralla para así poseer de unos planos más actualizados que complementen los ya hechos en su día y que por tanto han quedado desfasados debido a la metamorfosis que ha experimentado, especialmente, la zona en la que ahora yace El Batel. El proyecto está ubicado en la ciudad de Cartagena cuyo emplazamiento es el Auditorio El Batel, Paseo...

El plátano verde en la matriz productiva de la zona 8 de Ecuador.

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Rubén D. Paz Morales

2015-11-01

Full Text Available Ecuador con la Constitución de 2008 sentó las bases para la matriz productiva como nuevo modelo de desarrollo en el Ecuador, y con ello se creó todo un andamiaje de instituciones, reglamentos y créditos de largo plazo que apunten a desarrollar armónicamente las empresas ya existentes y a crear nuevos emprendimientos con el fin de aprovechar la materia prima existente en el país. La creación de las zonas de desarrollo por la SENPLADES fue fundamental para organizar por número de habitantes cada una de ellas. La zona 8 conformada por Guayaquil, Durán y Samborondón, es una de las de mayor dinamismo comercial. El Proyecto IC-ULVR 13-19 presenta una investigación exploratoria sobre los derivados del plátano verde en la matriz productiva, para cuyo fin se aplicó una observación guiada a autoservicios de la zona y una encuesta online para conocer los gustos y preferencias de los consumidores.

Inhibition of phospholipase A2 from human plasma by sodium bisulfite

International Nuclear Information System (INIS)

Wiggins, C.W.; Franson, R.C.

1987-01-01

The anti-oxidant sodium bisulfite has been shown to inhibit acid active(lysosomal), non-Ca ++ -dependent phospholipase A 2 (PLA 2 ), and to interact reversibly with unsaturated fatty acids, altering their chromatographic mobility. The authors examined the effect of bisulfite on neutral active, Ca ++ -dependent PLA 2 from human plasma. Using [1- 14 C]oleate-labelled autoclaved E. coli as substrate, PLA 2 activity was inhibited in a dose-dependent manner by bisulfite. Maximal inhibition occurred at 100μM bisulfite. Preincubation of plasma for 0-30 minutes with bisulfite resulted in a time-dependent increase in PLA 2 inhibition. Preincubation of substrate with bisulfite had no such effect. When the plasma PLA 2 was purified 25-fold by SP-Sephadex chromatography it was no longer inhibited by bisulfite. The SP-Sephadex wash through fraction, which contained greater than 95% of the applied protein but not PLA 2 activity, did not inhibit the purified enzyme. When incubated with bisulfite however, the SP-wash through fraction produced dose-dependent inhibition of the purified enzyme. These results indicate that sodium bisulfite inhibits human plasma PLA 2 , in vitro, indirectly by interaction with a factor(s) present in plasma and suggests that anti-oxidants may similarly influence expression of extracellular PLA 2 in vivo

Structural changes of the zona pellucida during fertilization and embryo development.

Science.gov (United States)

Familiari, Giuseppe; Heyn, Rosemarie; Relucenti, Michela; Sathananthan, Henry

2008-05-01

The zona pellucida (ZP) is a unique extracellular coat surrounding the maturing oocyte, during ovulation, fertilization, and early embryo development. It is formed by three/four glycoproteins. Ultrastructural data obtained with transmission (TEM) and scanning electron microscopy (SEM) were compared with molecular data on the glycoproteins network from ovulation to blastocyst formation. Molecular models are quite different to the morphology obtained with TEM, which shows a microfibrillar architecture, or with SEM, which shows a spongy or smooth surface. The saponin-ruthenium red-osmium tetroxide-thiocarbohydrazide technique allows to show the ZP real microfilamentous structure and the related functional changes. These results support an ultrastructural supramolecular model, more similar and comparable to molecular models related with the glycoprotein network. A detailed mapping of single mammalian ZP proteins and their relationship within the supramolecular architecture of the zona matrix would clearly supply insights into the molecular basis of sperm-egg recognition. Differences in ZP glycoproteins among mammals do not affect structural morphology; further studies are needed to clarify the relationships between ultrastructural and molecular organizations.

SGLT2 inhibition in the diabetic kidney – an update

Science.gov (United States)

Novikov, Aleksandra; Vallon, Volker

2016-01-01

Purpose of review The sodium glucose cotransporter SGLT2 reabsorbs most of the glucose filtered by the kidneys. SGLT2 inhibitors reduce glucose reabsorption thereby lowering blood glucose levels and have been approved as new anti-hyperglycemic drugs. While the therapeutic strategy is very promising, many questions remain. Recent findings Using validated antibodies SGLT2 expression was localized to the brush border of the early proximal tubule in human kidney and was found upregulated in genetic murine models of type 1 and 2 diabetes. SGLT2 may functionally interact with the Na/H exchanger NHE3 in the proximal tubule. SGLT1-mediated reabsorption explains the fractional glucose reabsorption of 40–50% during SGLT2 inhibition. SGLT2 is expressed on pancreatic alpha cells where its inhibition induces glucagon secretion. SGLT2 inhibition lowers GFR in hyperfiltering diabetic patients consistent with the tubular hypothesis of diabetic hyperfiltration. New data indicate a potential of SGLT2 inhibition for renal medullary hypoxia and ketoacidosis, but also for blood glucose effect-dependent and independent nephroprotective actions, renal gluconeogenesis inhibition, reduction in cardiovascular mortality, and cancer therapy. Summary The findings expand and refine our understanding of SGLT2 and its inhibition, have relevance for clinical practice, and will help interpret ongoing clinical trials on the long-term safety and cardiovascular effects of SGLT2 inhibitors. PMID:26575393

Zona residencial, en Leysin (Suiza

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Weber, M. R.

1965-05-01

Full Text Available This holiday residential area at Leysin is very much in the new style of tourist development centres. The present project involves 20 apartments, each of which can house a family of four or five persons. Each unit has three main rooms, a bathroom and a small kitchen. This residential complex also includes a house for the porter. The auxiliary services are also installed in the same building, namely: reception office, stores, washing equipment and central heating.Por su planeamiento, la zona residencial de vacaciones de Leysin se sitúa en la nueva tendencia del turismo social. El conjunto realizado agrupa 20 apartamentos, con capacidad para alojar familias de cuatro a cinco personas durante algunas semanas. Cada unidad consta de tres habitaciones principales, cuarto de baño y una pequeña cocina. Completa este conjunto residencial una edificación que aloja la vivienda del conserje, y los servicios comunes: recepción, almacén, lavadero y central de calefacción.

El Cultivo del Caucho y su Establecimiento en la Zona de Porce II

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Bustamante Betancur Orlando

1994-09-01

Full Text Available En este trabajo se presenta un estudio detallado de los suelos y clima de la región que comprende el proyecto hidroeléctrico Porce II de las Empresas Públicas de Medellín, comparativo con las condiciones que tienen las zonas caucheras del país y del mundo, con el fin de determinar las áreas aptas para el establecimiento de una explotación comercial. Se encontró que los requerimientos de clima y suelo del caucho están dentro de los parámetros que tiene la zona y de acuerdo con otras restricciones de pendiente y pedregosidad, se seleccionaron 1990 hectáreas para su establecimiento, distribuidas a lo largo y ancho de la cuenca hidrográfica. También se presenta en este artículo una descripción de las prácticas agronómicas del cultivo del caucho y las condiciones de manejo, propias para la zona estudiada. Se dan recomendaciones para las diferentes etapas relacionadas con la propagación y la producción de material vegetal (semillero, jardín clonal y vivero, la siembra y la explotación durante el período productivo de la plantación establecida. Finalmente se contemplan algunos aspectos sobre costos por actividades, la producción promedio de caucho seco y los ingresos en valores por hectárea año que genera el cultivo.

Inhibition of matrix metalloproteinase-2 by PARP inhibitors

International Nuclear Information System (INIS)

Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D.; Pacher, Pal; Schulz, Richard

2009-01-01

Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC 50 values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

Inhibition of matrix metalloproteinase-2 by PARP inhibitors

Energy Technology Data Exchange (ETDEWEB)

Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D. [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada); Pacher, Pal [National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, Bethesda, MD (United States); Schulz, Richard, E-mail: richard.schulz@ualberta.ca [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada)

2009-10-02

Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC{sub 50} values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

NARCIS (Netherlands)

Giepmans, B N; Moolenaar, W H

1998-01-01

Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

LIMITES URBANOS DE UNA ZONA TIPICA LA SERENA

OpenAIRE

Fernando Glasinovic Duhalde

2013-01-01

La ciudad de la Serena vive hoy Llna compleja crisis de crecimiento. Se duplican sus habitantes cada 30 .lúas, pero es(;"Í dejando vacío el casco histótico. ¿Seguirá extendiéndose ilimitadamente o crecerá "desde dentro" ocupando grandes manzanas edificadas pero vacías de gente. Este trabajo, que no es la historia de una acción terminada sino más bien la relación de su inicio, revisa aspectos relevantes a considerar en la delimitación de la Zona Típica de la Ciudad, comenzando el análisis desd...

Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling.

Science.gov (United States)

Feener, Edward P; Rosario, Felicia; Dunn, Sarah L; Stancheva, Zlatina; Myers, Martin G

2004-06-01

Jak family tyrosine kinases mediate signaling by cytokine receptors to regulate diverse biological processes. Although Jak2 and other Jak kinase family members are phosphorylated on numerous sites during cytokine signaling, the identity and function of most of these sites remains unknown. Using tandem mass spectroscopic analysis of activated Jak2 protein from intact cells, we identified Tyr(221) and Tyr(570) as novel sites of Jak2 phosphorylation. Phosphorylation of both sites was stimulated by cytokine treatment of cultured cells, and this stimulation required Jak2 kinase activity. While we observed no gross alteration of signaling upon mutation of Tyr(221), Tyr(570) lies within the inhibitory JH2 domain of Jak2, and mutation of this site (Jak2(Y570F)) results in constitutive Jak2-dependent signaling in the absence of cytokine stimulation and enhances and prolongs Jak2 activation during cytokine stimulation. Mutation of Tyr(570) does not alter the ability of SOCS3 to bind or inhibit Jak2, however. Thus, the phosphorylation of Tyr(570) in vivo inhibits Jak2-dependent signaling independently of SOCS3-mediated inhibition. This Tyr(570)-dependent mechanism of Jak2 inhibition likely represents an important mechanism by which cytokine function is regulated.

Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

International Nuclear Information System (INIS)

Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

1992-01-01

Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

Tiger, Bengal and Domestic Cat Embryos Produced by Homospecific and Interspecific Zona-Free Nuclear Transfer.

Science.gov (United States)

Moro, L N; Jarazo, J; Buemo, C; Hiriart, M I; Sestelo, A; Salamone, D F

2015-10-01

The aim of this study was to evaluate three different cloning strategies in the domestic cat (Felis silvestris) and to use the most efficient to generate wild felid embryos by interspecific cloning (iSCNT) using Bengal (a hybrid formed by the cross of Felis silvestris and Prionailurus bengalensis) and tiger (Panthera tigris) donor cells. In experiment 1, zona-free (ZP-free) cloning resulted in higher fusion and expanded blastocyst rates with respect to zona included cloning techniques that involved fusion or injection of the donor cell. In experiment 2, ZP-free iSCNT and embryo aggregation (2X) were assessed. Division velocity and blastocyst rates were increased by embryo aggregation in the three species. Despite fewer tiger embryos than Bengal and cat embryos reached the blastocyst stage, Tiger 2X group increased the percentage of blastocysts with respect to Tiger 1X group (3.2% vs 12.1%, respectively). Moreover, blastocyst cell number was almost duplicated in aggregated embryos with respect to non-aggregated ones within Bengal and tiger groups (278.3 ± 61.9 vs 516.8 ± 103.6 for Bengal 1X and Bengal 2X groups, respectively; 41 vs 220 ± 60 for Tiger 1X and Tiger 2X groups, respectively). OCT4 analysis also revealed that tiger blastocysts had higher proportion of OCT4-positive cells with respect to Bengal blastocysts and cat intracytoplasmic sperm injection blastocysts. In conclusion, ZP-free cloning has improved the quality of cat embryos with respect to the other cloning techniques evaluated and was successfully applied in iSCNT complemented with embryo aggregation. © 2015 Blackwell Verlag GmbH.

APLICACIÓN DE MAPAS DE KOHONEN PARA LA PRIORIZACIÓN DE ZONAS DE MERCADO: UNA APROXIMACIÓN PRÁCTICA

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Harol Mauricio Gámez Albán

Full Text Available Este artículo presenta una metodología basada en redes neuronales para realizar priorización de zonas de mercado visto desde un enfoque empresarial. En esta investigación se intenta dar solución a la incertidumbre que existe en la mayoría de las organizaciones en torno a la prioridad que tiene una zona de mercado; para ello se hace una búsqueda de los criterios más relevantes que las empresas tienen en cuenta para asignar prioridades a ciertos clientes. La problemática se sustenta por la ausencia de herramientas que permitan determinar la prioridad de una zona de mercado y la falta de una interrelación efectiva entre los departamentos de logística y mercadeo. Para ello se ocupan los mapas de Kohonen que son un tipo de red neuronal que facilita el agrupamiento de clientes y permiten determinar cuáles de ellos son los que impactan con mayor frecuencia los criterios de priorización previamente establecidos. Finalmente, se presentan tres escenarios con fin de validar la propuesta formulada y ver qué comportamiento tienen las redes neuronales en temas de priorización de zonas de mercado.

Dinâmica Glacial e Características Sedimentares Resultantes na Zona Proglacial da Geleira Ecology-Baía do Almirantado, Ilha Rei George Antártica.

OpenAIRE

Kátia Kellem Rosa; Rosemary Vieira; Jefferson Cardia Simões

2006-01-01

A geleira Ecology, localizada na ilha Rei George, ilhas Shetlands do Sul, está sofrendo um processo de rápida retração ao longo das últimas décadas, sendo que no período de 1956 a 1992/95 a geleira retrocedeu 0,37 Km2. Isto gerou um ambiente de deglaciação, com a exposição de várias geoformas na zona proglacial. Este trabalho objetiva estudar o ambiente de deglaciação da zona proglacial da geleir...

Prostaglandin E(2) synthase inhibition as a therapeutic target.

Science.gov (United States)

Iyer, Jitesh P; Srivastava, Punit K; Dev, Rishabh; Dastidar, Sunanda G; Ray, Abhijit

2009-07-01

Most NSAIDs function by inhibiting biosynthesis of PGE(2) by inhibition of COX-1 and/or COX-2. Since COX-1 has a protective function in the gastro-intestinal tract (GIT), non-selective inhibition of both cycloxy genases leads to moderate to severe gastro-intestinal intolerance. Attempts to identify selective inhibitors of COX-2, led to the identification of celecoxib and rofecoxib. However, long-term use of these drugs has serious adverse effects of sudden myocardial infarction and thrombosis. Drug-mediated imbalance in the levels of prostaglandin I(2) (PGI(2)) and thromboxane A(2) (TXA(2)) with a bias towards TXA(2) may be the primary reason for these events. This resulted in the drugs being withdrawn from the market, leaving a need for an effective and safe anti-inflammatory drug. Recently, the focus of research has shifted to enzymes downstream of COX in the prosta glandin biosynthetic pathway such as prostaglandin E(2) synthases. Microsomal prostaglandin E(2) synthase-1 (mPGES-1) specifically isomerizes PGH(2) to PGE(2), under inflammatory conditions. In this review, we examine the biology of mPGES-1 and its role in disease. Progress in designing molecules that can selectively inhibit mPGES-1 is reviewed. mPGES-1 has the potential to be a target for anti-inflammatory therapy, devoid of adverse GIT and cardiac effects and warrants further investigation.

Petrología de las rocas plutónicas de afinidad ofiolítica presentes en la zona de Cayo Grande (macizo ofiolítico Moa-Baracoa, Cuba Oriental

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Gerardo Orozco-Melgar

2001-03-01

Full Text Available La zona de Cayo Grande es parte del Macizo Moa-Baracoa, localizado en la parte más oriental de la faja Mayarí-Baracoa. En este trabajo se presentan y se discuten las características texturales, petrográficas, de quimismo mineral, de geotermometría catiónica, así como las implicaciones petrogenéticas de las rocas de afinidad ofiolítica presentes en la zona de Cayo Grande. Las características microestructurales de las dunitas impregnadas en la zona de estudio, indican condiciones de desequilibrio entre el olivino y la asociación plagioclasa+clinopiroxeno, y no presentan correlación entre los contenidos de forsterita y los de Ni en los olivinos. Esto es indicativo de la existencia de circulación magmática mediante flujo poroso en la zona. El orden de cristalización de los clinopiroxenos anterior a la plagioclasa, y la composición de las plagioclasas en las gabronoritas estudiadas en la zona de Cayo Grande, son indicativos de secuencias de acumulados en ofiolitas de zonas de suprasubducción, lo que sugiere un ambiente geodinámico en una zona de expansión de una cuenca de trasarco para las gabronoritas de la zona de Cayo Grande

Prostaglandin E 2 (PgE 2 ) Inhibition By Crude Extracts Of Selected ...

African Journals Online (AJOL)

This study was undertaken to assess anti-inflammatory activity of crude extracts of Cassine transvaalensis Burtt-Davy, Clerodendrum uncinatum Schinz and Commiphora glandulosa Schinz using COX inhibition assay. Water extract of C. transvaalensis root bark (125mg/ml) exhibited a (90%) PGE2 inhibition in ...

Pérdidas de suelo y nutrientes bajo diferentes coberturas vegetales en la zona Andina de Colombia

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J. Alexander Rodríguez

2009-07-01

Full Text Available El estudio se realizó en la reserva natural El Ciprés, ubicada en la vereda Bellavista, municipio de El Dovio (Valle del Cauca. La vereda se encuentra en la zona Andina de la cordillera occidental, en el departamento del Valle del Cauca, entre 1700 y 1800 m.s.n.m., con una temperatura promedio de 18 °C. Según la clasificación climática de Holdridge, corresponde a una zona de bosque húmedo Montano Bajo, con una precipitación promedio entre 2500 y 2700 mm/año, una humedad relativa de 90% y una pendiente del suelo de 62%. Las mediciones se hicieron en parcelas de escorrentía de 32 m² cada una y siete tipos de coberturas: guadua (Guadua angustifolia Kunth, bosque secundario, pastura (Brachiaria decumbens, café (Coffea arabica; banco de proteína (Trichanthera gigantea, caña forrajera (Saccharum officinarum y cultivo limpio conformado por yuca (Manihot esculenta, maíz (Zea mays y arracacha (Arracacia zanthorrhiza Brancroft. Para la evaluación se midieron las pérdidas de suelo y los nutrientes calcio, magnesio, potasio y fósforo en un periodo de 7 meses. Los resultados mostraron diferencias (P < 0.05 entre las coberturas evaluadas. Las pérdidas más altas de suelo y nutrientes ocurrieron bajo cultivos limpios (2.61 t/ha y las más bajas en guadua (0.08 t/ha. Estos resultados sugieren ventajas de los bosques de guadua en esta zona de Colombia, ya que además de contribuir a la conservación de los suelos y al mantenimiento de la fertilidad, es una alternativa económica complementaria para los productores rurales a partir de su manejo y aprovechamiento.

Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

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Kathryn L McCabe

Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1 and Na+/K+ATPaseα1 (ATPA1 on the apical surface in monolayer culture, and produced the key proteins of Descemet's membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2. Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis.hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium.

Selected Phytochemicals and Culinary Plant Extracts Inhibit Fructose Uptake in Caco-2 Cells.

Science.gov (United States)

Lee, Yurim; Lim, Yeni; Kwon, Oran

2015-09-18

This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [(14)C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5- and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5- and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition.

Geolog??a de la extremidad oriental de la zona sudportuguesa

OpenAIRE

Simancas Cabrera, Jos?? Fernando

1983-01-01

Se ha efectuado un estudio de geolog??a regional en la extremidad oriental de la zona Sudportuguesa estableci??ndose nuevas unidades litoestratigr??ficas en los materiales del devonico superior y carbon??fero inferior y en la cuenca del Viar. Se han estudiado los caracteres mineral??gicos y geoqu??micos del vulcanismo pretect??nico del plutonismo sin-postect??nico y del vulcanismo tardiherciano y se han establecido las deformaciones de plegamiento y la existencia de una notable cizalla fr??gi...

Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

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Yi-Rang Na

Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

Inhibiting glycogen synthase kinase-3 and transforming growth factor-β signaling to promote epithelial transition of human adipose mesenchymal stem cells.

Science.gov (United States)

Setiawan, Melina; Tan, Xiao-Wei; Goh, Tze-Wei; Hin-Fai Yam, Gary; Mehta, Jodhbir S

2017-09-02

This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip ® Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFβ signaling. It can be an adult stem cell source for epithelial cell-based therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Diet of Phyllodactyllus reissi (Sauria:Gekkonidae in the Zona Reservada de Tumbes, Peru

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Juan C. Jordán

2006-10-01

Full Text Available The purpose of this paper is to describe the diet of Phyllodactylus reissi, a nocturnal common gecko distributed from southern Ecuador to central Perú. A total of 15 individuals were captured inside buildings at Quebrada Faical, El Caucho and Bocana Murciélago in the Zona Reservada de Tumbes. Coleoptera and Blattoptera were the dominant preys from a total of six prey types found in stomachs. The number of prey per stomach were between 1 to 9, with 3 preys in average; the prey length average was 8,98 mm with a range of 1 to 25mm; the prey volume average was 61,97 mm3 with a range of 0,13 to 670,8 mm3 . The snout-vent length and snout length were not significantly related with average prey lengths and volumes. Phyllodactylus reissi has generalist habits with respect to diet and shows a tendency to consume medium-sized preys in the Zona Reservada de Tumbes.

Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiol

International Nuclear Information System (INIS)

Hagen, Thilo; D'Amico, Gabriela; Quintero, Marisol; Palacios-Callender, Miriam; Hollis, Veronica; Lam, Francis; Moncada, Salvador

2004-01-01

2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and proapoptotic activity. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1α (HIF1α) and to induce apoptosis in tumour cells by generating reactive oxygen species (ROS). In this study we report that 2ME2 inhibits mitochondrial respiration in both intact cells and submitochondrial particles, and that this effect is due to inhibition of complex I of the mitochondrial electron transport chain (ETC). The prevention by 2ME2 of hypoxia-induced stabilisation of HIF1α in HEK293 cells was found not to be due to an effect on HIF1α synthesis but rather to an effect on protein degradation. This is in agreement with our recent observation using other inhibitors of mitochondrial respiration which bring about rapid degradation of HIF1α in hypoxia due to increased availability of oxygen and reactivation of prolyl hydroxylases. The concentrations of 2ME2 that inhibited complex I also induced the generation of ROS. 2ME2 did not, however, cause generation of ROS in 143B rho - cells, which lack a functional mitochondrial ETC. We conclude that inhibition of mitochondrial respiration explains, at least in part, the effect of 2ME2 on hypoxia-dependent HIF1α stabilisation and cellular ROS production. Since these actions of 2ME2 occur at higher concentrations than those known to inhibit cell proliferation, it remains to be established whether they contribute to its therapeutic effect

Application of the Zona-Free Manipulation Technique to Porcine Somatic Nuclear Transfer

DEFF Research Database (Denmark)

Booth, Paul J; Tan, Shijian J; Holm, Peter

2001-01-01

cytoplast was agglutinated to a single granulosa cell (primary cultures grown in 0.5% serum for 2-5 days prior to use) in phytohaemagglutinin-P. Subsequently, each half cytoplast-granulosa cell couplet was simultaneously electrofused together and to another half cytoplast. Reconstructed embryos were...... activated in calcium ionophore A23187 followed by DMAP and were then individually cultured in microwells in NCSU-23 medium. On day 7 after activation, blastocyst yield and total cell numbers were counted. Of 279 attempted reconstructed NT embryos, 85.0 +/- 2.8% (mean +/- SEM; n = 5 replicates) successfully...... fused and survived activation. The blastocyst rate (per successfully fused and surviving embryo) was 4.8 +/- 2.3% (11/236; range, 0-12.8. Total blastocyst cell count was 36.0 +/- 4.5 (range, 18-58 cells). The blastocyst rate and total cell numbers of parthenogenetically activated and zona-free control...

Glucocorticoids inhibit the proliferation of IL-2-dependent T cell clones

International Nuclear Information System (INIS)

Fresno, M.; Redondo, J.M.; Lopez-Rivas, A.

1986-01-01

It has been shown that glucocorticoids inhibit mitogen or antigen-induced lymphocyte proliferation by decreasing the production of interleukin-2 (IL-2). They have studied the effect of dexamethasone (Dx) on the proliferation of IL-2-dependent T cell clones. They have found that preincubation of these clones with Dx inhibits ( 3 H) thymidine incorporation and cell proliferation in a dose-dependent manner (ID 50 % 5 x 10 -10 M). The inhibition of DNA synthesis by Dx was dependent on the concentration of IL-2. High concentration of IL-2 reversed completely this inhibition. The action of Dx seems to be mediated through the induction of a protein since the simultaneous presence of cycloheximide and Dx prevented the inhibitory effect of the latter. Moreover, dialyzed conditioned medium of Dx treated cells inhibited DNA synthesis by T cell clones. The biochemical characterization of this protein is in progress

Characterization of cell surface polypeptides of unfertilized, fertilized, and protease-treated zona-free mouse eggs

International Nuclear Information System (INIS)

Boldt, J.; Gunter, L.E.; Howe, A.M.

1989-01-01

The polypeptide composition of unfertilized, fertilized, and protease-treated zona-free mouse eggs was evaluated in this study. Zona-free eggs were radioiodinated by an Iodogen-catalyzed reaction. Light microscopic autoradiography of egg sections revealed that labeling was restricted to the cell surface. Labeled eggs were solubilized, and cell surface polypeptides were identified by one-dimensional SDS polyacrylamide gel electrophoresis and autoradiography. The unfertilized egg demonstrated 8-10 peptides that incorporated 125 I, with major bands observed at approximately 145-150, 94, and 23 kilodaltons (kD). Zona-free eggs fertilized in vitro and then radiolabeled demonstrated several new bands in comparison to unfertilized eggs, with a major band appearing at approximately 36 kD. Treatment of radiolabeled unfertilized eggs with either trypsin or chymotrypsin (1 mg/ml for 5-20 min) caused enzyme-specific modifications in labeled polypeptides. Trypsin (T) treatment resulted in time-dependant modification of the three major peptides at 145-150, 94, and 23 kD. Chymotrypsin (CT) treatment, in contrast, was associated with loss or modification of the 94 kD band, with no apparent effect on either the 145-150 or 23 kD band. Taken together with previous data indicating that T or CT egg treatment interferes with sperm-egg attachment and fusion, these results suggest a possible role for the 94 kD protein in sperm-egg interaction

Agroturismo y desarrollo rural: situación actual, potencial y estrategias en zonas de montaña del Sureste español

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Samir Sayadi

2001-01-01

Full Text Available En el presente trabajo, tras ofrecer algunos aspectos conceptuales sobre el agroturismo, se comentan los principales resultados de un análisis de la situación y perspectivas de la actividad agroturística en la zona más oriental de la parte alta de la comarca granadina de Las Alpujarras. Estos resultados han sido obtenidos, principalmente, mediante encuestas y entrevistas a visitantes y agricultores de la zona. Posteriomente, se ofrecen algunas conclusiones y, a partir de ellas, se perfilan estrategias con el fin de aprovechar el potencial recreativo de los sistemas agrarios para el desarrollo rural integrado, endógeno y sostenible de la zona estudiada.

Inhibition of osteoclast differentiation by overexpression of NDRG2 in monocytes

Energy Technology Data Exchange (ETDEWEB)

Kang, Kyeongah; Nam, Sorim; Kim, Bomi; Lim, Ji Hyun; Yang, Young; Lee, Myeong-Sok; Lim, Jong-Seok, E-mail: jslim@sookmyung.ac.kr

2015-12-25

N-Myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family of differentiation-related genes, has been characterized as a regulator of dendritic cell differentiation from monocytes, CD34{sup +} progenitor cells, and myelomonocytic leukemic cells. In this study, we show that NDRG2 overexpression inhibits the differentiation of U937 cells into osteoclasts in response to stimulation with a combination of macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-κB ligand (RANKL). U937 cells stably expressing NDRG2 are unable to differentiate into multinucleated osteoclast-like cells and display reduced tartrate-resistant acid phosphatase (TRAP) activity and resorption pit formation. Furthermore, NDRG2 expression significantly suppresses the expression of genes that are crucial for the proliferation, survival, differentiation, and function of osteoclasts, including c-Fos, Atp6v0d2, RANK, and OSCAR. The activation of ERK1/2 and p38 is also inhibited by NDRG2 expression during osteoclastogenesis, and the inhibition of osteoclastogenesis by NDRG2 correlates with the down-regulation of the expression of the transcription factor PU.1. Taken together, our results suggest that the expression of NDRG2 potentially inhibits osteoclast differentiation and plays a role in modulating the signal transduction pathway responsible for osteoclastogenesis. - Highlights: • The expression of NDRG2 significantly impairs osteoclast differentiation. • PU.1 and p38 MAPK inhibitions by NDRG2 are critical for the inhibition of osteoclastogenesis. • Knockdown of NDRG2 rescues the ability of monocytes to differentiate into osteoclasts. • NDRG2 expression in BM and primary macrophages also impairs osteoclast differentiation. • This study implies the potential of NDRG2 expression in the inhibition of osteoclastogenesis.

2-(1H-Benzimidazol-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol, a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition

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Jin Liu

2014-10-01

Full Text Available In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2 production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.

Enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7.

Science.gov (United States)

Fang, Zhong-Ze; Wang, Haina; Cao, Yun-Feng; Sun, Dong-Xue; Wang, Li-Xuan; Hong, Mo; Huang, Ting; Chen, Jian-Xing; Zeng, Jia

2015-03-01

UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation conjugation reaction plays an important role in the elimination of many important clinical drugs and endogenous substances. The present study aims to investigate the enantioselective inhibition of carprofen towards UGT isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation mixture was used to screen the inhibition potential of (R)-carprofen and (S)-carprofen towards multiple UGT isoforms. The results showed that (S)-carprofen exhibited stronger inhibition potential than (R)-carprofen towards UGT2B7. However, no significant difference was observed for the inhibition of (R)-carprofen and (S)-carprofen towards other UGT isoforms. Furthermore, the inhibition kinetic behavior was compared for the inhibition of (S)-carprofen and (R)-carprofen towards UGT2B7. A Lineweaver-Burk plot showed that both (S)-carprofen and (R)-carprofen exhibited competitive inhibition towards UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameter (Ki ) was calculated to be 7.0 μM and 31.1 μM for (S)-carprofen and (R)-carprofen, respectively. Based on the standard for drug-drug interaction, the threshold for (S)-carprofen and (R)-carprofen to induce a drug-drug interaction is 0.7 μM and 3.1 μM, respectively. In conclusion, enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7 was demonstrated in the present study. Using the in vitro inhibition kinetic parameter, the concentration threshold of (S)-carprofen and (R)-carprofen to possibly induce the drug-drug interaction was obtained. Therefore, clinical monitoring of the plasma concentration of (S)-carprofen is more important than (R)-carprofen to avoid a possible drug-drug interaction between carprofen and the drugs mainly undergoing UGT2B7-catalyzed metabolism. © 2014 Wiley Periodicals, Inc.

The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

Science.gov (United States)

Raff, H; Kohandarvish, S

1990-08-01

Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

NARCIS (Netherlands)

Petrykiv, Sergei; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.

Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer

AI-2 of Aggregatibacter actinomycetemcomitans Inhibits Candida albicans Biofilm Formation

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Endang W. Bachtiar

2014-07-01

Full Text Available Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium, and Candida albicans, a polymorphic fungus, are both commensals of the oral cavity but both are opportunistic pathogens that can cause oral diseases. A. actinomycetemcomitans produces a quorum-sensing molecule called autoinducer-2 (AI-2, synthesized by LuxS, that plays an important role in expression of virulence factors, in intra- but also in interspecies communication. The aim of this study was to investigate the role of AI-2 based signaling in the interactions between C. albicans and A. actinomycetemcomitans. A. actinomycetemcomitans adhered to C. albicans and inhibited biofilm formation by means of a molecule that was secreted during growth. C. albicans biofilm formation increased significantly when co-cultured with A. actinomycetemcomitans luxS, lacking AI-2 production. Addition of wild-type-derived spent medium or synthetic AI-2 to spent medium of the luxS strain, restored inhibition of C. albicans biofilm formation to wild-type levels. Addition of synthetic AI-2 significantly inhibited hypha formation of C. albicans possibly explaining the inhibition of biofilm formation. AI-2 of A. actinomycetemcomitans is synthesized by LuxS, accumulates during growth and inhibits C. albicans hypha- and biofilm formation. Identifying the molecular mechanisms underlying the interaction between bacteria and fungi may provide important insight into the balance within complex oral microbial communities.

Manejo de Sigatoka negra (Mycosphaerella Fijiensis var. Difformis Morelet en plátano cv. “Curraré” en San Carlos, Zona Norte

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Carlos Muñoz Ruiz

2006-05-01

Full Text Available Se evaluaron los diferentes productos químicos, utilizados en el control de Sigatoka negra en banano, en el cultivo de plátano, en la zona de Santa Clara de San Carlos. Uno de los principales objetivos fue generar un programa de manejo químico de la enfermedad para la zona de San Carlos, posible de ser transferido a otras zonas plataneras del país; el otro objetivo fue establecer las bases para automatizar las actividades culturales de manejo de plantaciones de musáceas, mediante la creación de un Software para computadora y asequible por internet.

Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

Science.gov (United States)

Bruick, Richard K.; Caldwell, Charles G.; Frantz, Doug E.; Gardner, Kevin H.; MacMillan, John B.; Scheuermann, Thomas H.; Tambar, Uttam K.

2017-09-12

Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

Determinación de zonas agroclimáticas para la producción de mango (Mangifera indica L. “Manila” en Veracruz, México

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Jorge Luis Martínez Fonseca

2012-02-01

Full Text Available El mango (Mangifera indica L. es un frutal de importancia económica en México, en el 2004 se reportaron 166 000 ha plantadas en más de once estados del país, en el estado de Veracruz 25 550 ha, donde el 85% es de la variedad “Manila”. El objetivo de este trabajo fue determinar las regiones agroclimáticas para el cultivo de mango “Manila” en el estado de Veracruz, México, por medio del Análisis de Componentes Principales (ACP con variables climatológicas (temperatura, precipitación, evaporación y radiación solar, además se elaboraron gráficas hidro-termales (relacionando: precipitación total y temperatura mínima mensual. Del ACP se derivaron dos vectores asociados con la temperatura mínima anual y precipitación total anual, que juntos explican el 83% de la variación climática total entre las localidades productoras de mango “Manila”; se definieron dos grupos de localidades con agroclimas diferentes, mismos que se confirmaron con las gráficas hidro-termales; con apoyo de información bibliográfica y de productividad, se definieron tres zonas de aptitud agroclimáticas para el cultivo de mango “Manila”, con los siguientes intervalos de variación de la temperatura mínima anual: zona 1 (No Apta menor de 13.5° C; zona 2 (Apta de 13.5 a 17.5° C; zona 3 (Moderadamente Apta de 17.5 a 23.0° C. Con un modelo empírico de temperatura mínima y un modelo de elevación digital, por medio de un sistema de información geográfica (SIG, se realizó la cartografía de las zonas geográficas con diferente grado de aptitud Agroclimática.

Implicaciones de la zona Ossa-Morena y dominios equivalentes en el modelo geodinámico de la Cadena Hercinica europea

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Castro, A.

1987-08-01

Full Text Available The Ossa-Morena zone (OMZ has some peculiar features clearly different from those of the other inner domains in the Iberic Hercynian chain. It is a continental domain (microcontinent ? attached, from Lower Paleozoic times, to the continental crust of the Central Iberian zone (CIZ. During the Hercynian collision (Upper Paleozoic the OMZ behaved in a way different form that of adjacent areas (CIZ due to the peculiar features (Iess thicknees and pre-Hercynian evolution (Ordovician rifting. The OMZ, and their equivalent domains in the Iberian peninsula as well as in European chain, can have strong implications on the evolution of the Hercynian orogene. Part of the OMZ crust (and equivalent domains, together with the oceanic crust developed within it during the Ordovician rifting, was obduced over the inner domains (CIZ in areas of frontal collision (e.g. NW Iberian peninsula and French Massif Central and strongly stretched in areas of oblique collision (e.g. OMZ of SW Iberian peninsula and North Armorican domains.La zona Ossa-Morena (ZOM del hercínico peninsular posee unas características peculiares que la diferencian netamente de los otros dominios internos de la Cadena. Se trata de un dominio cortical (microcontinente ? adosado a la corteza de la Zona Centro-Ibérica (ZCI desde el Paleozoico Inferior. Durante la colisión continental hercínica (Palezoico Superior la ZOM responde de diferente forma que las zonas adyacentes (ZCI debido a su diferente constitución (menor espesor y peculiar evolución prehercínica (rifting ordovícico. Esta zona y sus equivalentes en otros dominios del hercínico peninsular y europeo, tienen fuertes implicaciones en el desarrollo del orógeno hercínico. Parte de la corteza continental de la ZOM fue, junto con la corteza oceánica desarrollada localmente en su interior durante el rifting ordovícido, obducida sobre los dominios internos (ZCI en zonas de colisión frontal (e.g. NW peninsular y Macizo C�

Condiciones de vida en zonas palúdicas de Antioquia (Colombia, 2005 Condições de vida em zonas palúdicas de Antioquia (Colômbia, 2005 Living conditions in Antioquia's (Colombia paludic areas, 2005

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Jaime Carmona Fonseca

2010-07-01

Full Text Available Objetivo. Explorar las condiciones de vida de las familias de niños palúdicos en dos zonas de Antioquia. Metodología. Diseño descriptivo de corte transversal. Se describe y analiza un conjunto de variables socioeconómicas que expresan las condiciones de vida de esas familias, en 2004-2005. Resultados. 88 familias de los municipios de Turbo y El Bagre, el 58% vivían en zona. En general, las variables analizadas presentan diferencia estadísticamente significativa por municipio y zona (peores condiciones: Turbo-rural; menos malas: El Bagre-urbano. Los rasgos familiares más frecuentes fueron: familias nucleares típicas (66%, con un promedio de 7,1 miembros. Habitan rancho/tugurio el 29%, cuentan con servicio sanitario intradomicilio el 42%, tiraban las basuras a campo abierto el 31%. El 69% de las viviendas tienen peridomicilio con vegetación y otro 66% tiene agua estancada/ corriente. El padre trabajaba en 64%, el trabajo era inestable en el 59% de los casos; las ocupaciones más comunes fueron de agricultor (53%, minero (13% y jornalero (12%. El ingreso monetario mensual promedio era de solo $244 000. Hubo 58% de las familias con fuentes estables de alimentos. El consumo de carnes/vísceras animales fue menor de una 1 vez/semana, leche y huevos de 2-3 veces/semana, frutas ricas en carotenos provitamina A no se consumían. Los alimentos consumidos tenían alta probabilidad de satisfacer los requerimientos familiares de vitamina A en grado alto (45%. Conclusión. Las condiciones de vida de las familias que residen en Turbo y El Bagre son muy deficientes y es elevada la cantidad de familias con necesidades básicas no satisfechas. Hay importantes diferencias entre los municipios de estudio y entre la zona urbana y rural. La situación de mala calidad de vida en estas regiones maláricas supera ampliamente lo referido por los promedios para el departamento de Antioquia y para Colombia.Objetivo. Explorar as condições de vida das fam

Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2

International Nuclear Information System (INIS)

Ullrich, Nina D.; Koschak, Alexandra; MacLeod, Kenneth T.

2007-01-01

Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca 2+ channel (Ca v 1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca 2+ current, I CaL . The effect of oestrogen on I CaL was measured in Ca v 1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I CaL . Oestrogen (50 μM) rapidly reduced I CaL by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca 2+ channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I CaL through direct interaction of the steroid with the channel protein

Santiago Zona Árida: una arquitectura de la sombra

OpenAIRE

Pérez de Arce,Rodrigo

2004-01-01

¿El árbol urbano como mitigación? ¡Falso! Desmontando el sentido supuesto para el "impacto ambiental", tan usado por algunas corrientes actuales del urbanismo, Pérez de Arce reinvindica las zonas áridas del planeta como origen del jardín y la ciudad. A partir de la revisión de la incorporación del árbol en el espacio público santiaguino, la discusión se centra en la relación entre sequía, sombra, trazados y la capacidad del jardín y la arquitectura de generar una cualidad ambiental urbana....

Màquina omplidora semiautomàtica per zona ATEX

OpenAIRE

Tiñena Guiamet, Jaume

2014-01-01

En aquest projecte es realitza una màquina omplidora semiautomàtica per a zones ATEX (Appareils destinés à êtreutilisés en ATmosphères EXplosives). Aquesta màquina té la capacitat d’omplir tot tipus de recipients amb capacitats des de 20 fins a 1500 litres. Perquè aquest procés sigui possible, un sistema de transportadors desplaça el palet buit fins la zona de dosificació, lloc on l’operari posiciona manualment el dosificador per posteriorment iniciar el cicle d’emplenat automàtic. L’opera...

MEL-18 interacts with HSF2 and the SUMO E2 UBC9 to inhibit HSF2 sumoylation.

Science.gov (United States)

Zhang, Jie; Goodson, Michael L; Hong, Yiling; Sarge, Kevin D

2008-03-21

In a previous study we found that sumoylation of the DNA-binding protein heat shock factor 2 (HSF2) is up-regulated during mitosis, but the mechanism that mediates this regulation was unknown. Here we show that HSF2 interacts with the polycomb protein MEL-18, that this interaction decreases during mitosis, and that overexpression and RNA interference-mediated reduction of MEL-18 result in decreased and increased HSF2 sumoylation, respectively. Other results suggest that MEL-18 may also function to inhibit the sumoylation of other cellular proteins. The results also show that MEL-18 is able to interact with the small ubiquitin-like modifier (SUMO) ubiquitin carrier protein (E2) enzyme UBC9 and that MEL-18 inhibits the ability of UBC9 to transfer the SUMO protein to target proteins. Together, the results in this work suggest a mechanism in which MEL-18 bound to HSF2 inhibits its sumoylation by binding to and inhibiting the activity of UBC9 enzymes in the vicinity of HSF2. These results provide an explanation for how mitotic HSF2 sumoylation is regulated and suggest that MEL-18, in contrast to the sumoylation-stimulating activities of the polycomb protein PC2, actually functions like an anti-SUMO ubiquitin-protein isopeptide ligase (E3), interacting both with HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity to decrease sumoylation of a target protein, in this case that of HSF2.

Simulation of the shopping center 'Zona I' evacuation

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Jevtić Radoje B.

2014-01-01

Full Text Available One of the most important and the most complex tasks in human protection and human safety in objects is the projecting of the object evacuation. There are many factors that could effect on the opportune living of object such as object assignment, arrangement of rooms, arrangement of furniture, arrangement of exits, occupant speed and many other that human lives and material properties depend on. This is very important for objects with great number of humans, such as high residential objects, shopping centers, schools, hospitals etc. This paper has written to show the possible evacuation situations and calculate minimal time for evacuation in case of the shopping center 'Zona I' in Niš.

Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels.

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Xiao-Fei Gao

Full Text Available (+-SKF 10047 (N-allyl-normetazocine is a prototypic and specific sigma-1 receptor agonist that has been used extensively to study the function of sigma-1 receptors. (+-SKF 10047 inhibits K(+, Na(+ and Ca2+ channels via sigma-1 receptor activation. We found that (+-SKF 10047 inhibited Na(V1.2 and Na(V1.4 channels independently of sigma-1 receptor activation. (+-SKF 10047 equally inhibited Na(V1.2/1.4 channel currents in HEK293T cells with abundant sigma-1 receptor expression and in COS-7 cells, which barely express sigma-1 receptors. The sigma-1 receptor antagonists BD 1063,BD 1047 and NE-100 did not block the inhibitory effects of (+-SKF-10047. Blocking of the PKA, PKC and G-protein pathways did not affect (+-SKF 10047 inhibition of Na(V1.2 channel currents. The sigma-1 receptor agonists Dextromethorphan (DM and 1,3-di-o-tolyl-guanidine (DTG also inhibited Na(V1.2 currents through a sigma-1 receptor-independent pathway. The (+-SKF 10047 inhibition of Na(V1.2 currents was use- and frequency-dependent. Point mutations demonstrated the importance of Phe(1764 and Tyr(1771 in the IV-segment 6 domain of the Na(V1.2 channel and Phe(1579 in the Na(V1.4 channel for (+-SKF 10047 inhibition. In conclusion, our results suggest that sigma-1 receptor agonists directly inhibit Na(V1.2/1.4 channels and that these interactions should be given special attention for future sigma-1 receptor function studies.

Modelo agroecológico en la zona de amortiguamiento del Santuario de Flora y Fauna de Iguaque

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Javier Enrique Tovar-Puentes

2013-01-01

Full Text Available La zona de amortiguamiento del Santuario de Flora y Fauna de Iguaque viene siendo afectada por los residentes aledaños, que expanden la frontera agrícola y ejercen presión hacia el área protegida en busca de mejorar sus condiciones socio-económicas y la variedad de alimentos para la familia; situación que genera un conflicto socio-ambiental. Partiendo de la importancia que en la actualidad se le ha dado al tema ecológico y medioambiental, se ha considerado fundamental buscar alternativas concretas de manejo que muestren un impacto positivo desde los puntos de vista ambiental, social, económico y agroecológico, derivándose del aprovechamiento racional de los recursos ecológicos. Dentro de las múltiples alternativas planteadas por el Estado y los gobiernos sectoriales, se habla del desarrollo sostenible, un modelo innovador que permite desplegar políticas productivas desarrolladas incluso en ambientes protegidos por el Estado, caso en concreto, el predio “Buena Vista”, en la zona de amortiguamiento del Santuario de Flora y Fauna de Iguaque, en el municipio de Arcabuco; en este predio se realizó una planificación para zonificar y dividir las aéreas, determinando los tipos de producción agroecológica que se adapten a las características de la zona, identificando las labores que facilitan la ubicación de los diferentes sistemas productivos, y así establecer una cadena productiva familiar diferente al monocultivo de papa, que faciliten la mano de obra y repercutan en la actividad social de la comunidad y ambiental en la zona amortiguadora.

Variabilidad espacial y temporal de la temperatura del aire en la zona cafetera colombiana

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Edna Paola Pérez Rendón

2016-03-01

Full Text Available La zona cafetera colombiana está ubicada enteramente en el hemisferio norte, entre los 1 y 11° grados de latitud, sobre la cordillera de los Andes. Esta condición (ecuatorial andina ha hecho que se dé por sentado que la variación temporal de la temperatura es mínima y que por ello, en su mayor parte la variabilidad de este elemento es espacial, atribuible casi exclusivamente a los cambios en altura sobre el nivel del mar. En este estudio se exploran factores de variación alternas, que muestran cómo, además de la altitud, otros factores, como la latitud, la zona de convergencia intertropical, El Niño Oscilación del Sur y el Cambio Climático, inciden sobre esta variable climática, que a su vez ejerce un papel fundamental sobre las plantaciones de cafeto.

Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.

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Steffen Nyegaard

Full Text Available Secretory phospholipase A2 (sPLA2 is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.

Un método para la evaluación de riesgos para la salud en zonas mineras

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Mejía Jesús

1999-01-01

Full Text Available Objetivo. En este trabajo se propone un esquema de tres fases para evaluar el riesgo en salud en las zonas mineras. La validación del esquema se efectuó en una zona de San Luis Potosí, México. Material y métodos. El monitoreo incluyó análisis de metales en suelo superficial, polvo residencial y agua de pozos. La biodisponibilidad se midió como el nivel de arsénico urinario en niños de las áreas contaminadas. La evaluación toxicológica consistió en análisis de la hepatotoxicidad (niveles de aspartato transaminasa y neurotoxicidad (niveles de dopamina y de sus metabolitos en ratas tratadas con residuos mineros. Resultados. Se encontró contaminación por arsénico y plomo en suelo y polvo. La biodisponibilidad fue positiva: 71% de los niños analizados tuvieron niveles urinarios de arsénico por arriba del valor normal. Los estudios de toxicidad mostraron daño hepático y alteraciones neuroquímicas en las ratas tratadas con el residuo. Conclusiones. El método fue útil para demostrar el riesgo en salud y para que las autoridades decidieran instrumentar un programa de restauración en la zona.

Fertilización de pastos en zonas semiáridas de secano del S-W- español

OpenAIRE

Olea Márquez de Prado, L.; Jiménez Mozo, J.

2011-01-01

Se presentan los resultados de aportaciones de P, K, Mg + Ca, Mo + Mn y Cu + Co sobre pastizales artificiales de leguminosas + gramíneas y pastos naturales en varias zonas de Extremadura. En pastizales artificiales la fertilización previa al establecimiento con 75-95 u. de P2O5 /Ha, duplica la producción. En pastos naturales la fertilización anual con 46 u. de P2 O5, duplica la producción y el porcentaje de leguminosas. Los mayores incrementos se consiguen con aportaciones anuales de 40 u. de...

For the categories `east` and `west` in the stories `White Fortress` by Ohran Pamuk and Zona Zamfirova by Stevan Sremac

OpenAIRE

Karanikolova-Cocorovska, Lusi

2015-01-01

This article deals with the issues east - west in two novels: "White Fortress" by OrhanPamuk and "ZonaZamfirova" by StevanSremac. The focus is on the treatment of these two entities as separate categories, according to their significance in the novels, and also according to their importance to the culture of the East and West. It is determined the analysis of the categories "east" and "west" in the novels "White Fortress" by OrhanPamuk and ZonaZamfirova by StevanSremacod simply because t...

Estructura espacial de Eucinostomus argenteus (Pisces: Gerreidae en la zona norte del Caribe colombiano

Directory of Open Access Journals (Sweden)

Jorge Paramo

2010-01-01

Full Text Available Esta investigación se llevó a cabo para determinar la distribución espacial de la densidad (captura por unidad de área – CPUA y de la estructura de tallas de Eucinostomus argenteus y su relación con las variables ambientales en la zona norte del Caribe colombiano. Los datos fueron se tomaron durante un crucero de investigación realizado en  la época seca (febrero de 2006 entre  Puerto Estrella (La Guajira y Santa Marta (Magdalena. Las muestras biológicas se colectaron con una red de arrastre (en estratos de profundidad < 50 m y 50-100 m siguiendo un diseño de muestreo sistemático. Los individuos maduros y de tallas mayores se encontraron distribuidos principalmente entre Manaure y Punta Gallinas, donde la plataforma continental es muy ancha y la oceanografía local esta modulada por la surgencia estacional. Los peces juveniles, se distribuyeron al sur del área de estudio, entre Boca Camarones y el Río Buritaca, cerca de la costa. En este sector la plataforma es muy estrecha y con alta productividad biológica por la presencia de ríos, manglares y pastos marinos, sirviendo como zona de alimentación y refugio para E. argenteus. En general los resultados sugieren que las variables ambientales son importantes para la distribución espacial de la abundancia y las tallas de  E. argenteus en la zona norte del Caribe colombiano, siendo la temperatura y la profundidad las variables que predijeron mejor la distribución espacial de la especie.

Dimensión de competitividad urbana en la zona sur de Tamaulipas: el papel del gerente

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Javier Chávez Meléndez

2017-01-01

Full Text Available El Banco Interamericano de Desarrollo (BID desarrolló una metodología basada en una serie de indicadores denominada ICES (iniciativa de ciudades emergentes sustentables, que como primera etapa propone el diagnóstico de una ciudad o zona conurbada para poder planear las acciones futuras de mejora (BID, 2014. Este proyecto de investigación se sustentó en este modelo y en el modelo del IMCO. Para lo cual, se desarrolló una  investigación descriptiva, con enfoque cuantitativo basada en el desarrollo de la dimensión de competitividad urbana en la zona sur de Tamaulipas. Los resultados obtenidos se presentan y permiten generar un espacio de acciones de planeación, reflexión y de formulación de políticas públicas.

APLICACIONES DE LA TELEDETECCIÓN AL LEVANTAMIENTO DEL USO DE LA TIERRA EN LA ZONA CAFETALERA NORTE DE LA CIUDAD DE ALAJUELA, COSTA RICA

OpenAIRE

Hernández Z., Eduardo

2011-01-01

El presente es un trabajo de aplicación de la teledetección con el apoyo de la cartografía topográfica y de las fotografías aéreas para el levantamiento del uso del suelo en la zona cafetalera norte de la ciudad de Alajuela, Costa Rica.  La zona de estudio está situada en el Valle Central de Costa Rica.  Se trata de una zona agrícola destinada al cultivo del café, de la caña de azúcar, de pastos extensivos e intensivos y a la horticultura.  Las partes altas de montañas y cañones de ríos son c...

Caracterización y propuesta técnica de la acuacultura en la zona de chanduy, provincia del Guayas

OpenAIRE

Mejillones, Ronald; Ocaña, Luis; Vicuña, Jorge; Alvarez, Marcos

2009-01-01

Este trabajo tiene como objetivo describir la evolución y desarrollo de la acuacultura en la parroquia Chanduy, nos describe las características que identifican a la zona y como ésta se relaciona con la industria a nivel nacional y a través de una encuesta recopilamos información que nos permite proporcionar datos de producción, estrategias de manejo, además de un estimado del área dedicada a la acuacultura en la zona de estudio. Es así, que podemos decir que el sector de Chanduy se dedica p...

TGF-β2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

International Nuclear Information System (INIS)

Lu Jiawei; Lu Zhenyu; Reinach, Peter

2006-01-01

The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-β2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-β2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-β2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-β2 and FGF-2 oppositely affect BCE cell proliferation and TGF-β2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-β2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-β2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-β2-induced suppression of the PI3-kinase/AKT signaling pathway

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A.

Science.gov (United States)

Huang, Qiuyue; Qin, Shanshan; Yuan, Xiaoning; Zhang, Liang; Ji, Juanli; Liu, Xuewen; Ma, Wenjing; Zhang, Yunfei; Liu, Pengfei; Sun, Zhiting; Zhang, Jingxuan; Liu, Ying

2017-07-01

We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers. Atn-induced metastasis inhibition was associated with reactivation of PP2A, downregulation of CIP2A and Akt phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes the anti-metastasis effect induced by Atn. Our findings disclose the novel therapeutic mechanism of this targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

La economía ecológica y las formas de propiedad del manglar de la zona norte de Esmeraldas

OpenAIRE

Rosales Estupiñan, Mauricio

1995-01-01

Hay dos problemas urgentes por resolver en la zona norte de Esmeraldas: La pobreza de las comunidades locales, y la conversión (destrucción) de los manglares a camaroneras y sus externalidades. En la zona norte de Esmeraldas se encuentra el sistema de manglar comprendido entre los ríos Mataje y los alrededores de la desembocadura del río Santiago, con un extensión aproximada de 50.000 ha. Los manglares son un sistema ecológico abierto que interactúa con el mar, los estuarios, los esteros y la...

Migración y selectividad : estudio comparativo de zonas metropolitanas de gran atracción migratoria : Puerto Vallarta y Tijuana

OpenAIRE

Serna Enciso, Teresita de Jesús

2008-01-01

La localización de ciertos asentamientos humanos en lugares geográficos especiales como las fronteras territoriales y las costas marítimas, ha convertido a diversos poblados en grandes polos de atracción económica y migratoria. En este trabajo de investigación se muestra un estudio descriptivo y comparativo de la migración reciente hacia dos polos de gran atracción: la zona metropolitana de Puerto Vallarta y la zona metropolitana de Tijuana. De manera muy particular, se presenta el análisis d...

Sodium glucose transporter 2 (SGLT2 inhibition and ketogenesis

Directory of Open Access Journals (Sweden)

Sanjay Kalra

2015-01-01

Full Text Available Sodium glucose transporter 2 (SGLT2 inhibitors are a recently developed class of drug that have been approved for use in type 2 diabetes. Their unique extra-pancreatic glucuretic mode of action has encouraged their usage in type 1 diabetes as well. At the same time, reports of pseudo ketoacidosis and ketoacidosis related to their use have been published. No clear mechanism for this phenomenon has been demonstrated so far. This communication delves into the biochemical effects of SGLT2 inhibition, discusses the utility of these drugs and proposes steps to maximize safe usage of the molecules.

Leishmaniose tegumentar americana em centro de treinamento militar localizado na Zona da Mata de Pernambuco, Brasil American cutaneous leishmaniasis in military training unit localized in Zona da Mata of Pernambuco State, Brazil

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Sinval P. Brandão-Filho

1998-12-01

Full Text Available Um surto de leishmaniose tegumentar americana ocorreu em 1996 em unidade de treinamento militar situada na Zona da Mata de Pernambuco, com o registro de 26 casos humanos. Um inquérito epidemiológico foi realizado através da realização de levantamento entomológico e da aplicação do Teste de Montenegro. Lutzomyia choti apresentou predominância de 89,9% dos flebótomos identificados. De 545 homens que participaram de treinamentos no período, 24,1% (incluindo os casos clínicos foram positivo para o Teste de Montenegro.An outbreak of American cutaneous leishmaniasis has been occurred in military training unit localized in 'Zona da Mata' of Pernambuco State, Brazil, where were registered 26 human cases. An epidemiological survey was carried out by entomological investigation and Montenegro skin test (MST. Lutzomyia choti presents predominance (89.9% in sandflies identified. Out of 545 men who realized training activities were 24.12% positive to MST.

Role of photophosphorylation in SO/sub 2/ and SO/sub 3//sup 2 -/ inhibition of photosynthesis in isolated chloroplasts

Energy Technology Data Exchange (ETDEWEB)

Cerovic, Z G; Kalezic, R; Plesnicar, M

1982-01-01

Sulphur dioxide inhibits noncyclic photophosphorylation in isolated envelope-free chloroplasts. This inhibition was shown to be reversible and competitive with phosphate, with an inhibitor constant of K/sub i/ = 0.8 mM. The same inhibition characteristics were observed when phosphoglycerate (PGA)- or ribulose-1,5-bisphosphate (RuBP)- dependent oxygen evolution was examined in a reconstituted chloroplast system in the presence of SO/sub 3//sup 2 -/. Using an ATP-regenerating system (phosphocreatine-creatine kinase), it was demonstrated that the inhibition of PGA-dependent oxygen evolution is solely the result of inhibited photophosphorylation. It is concluded that at low SO/sub 2/ and SO/sub 3//sup 2 -/ concentrations the inhibition of photophosphorylation is responsible for the inhibition of photosynthetic oxygen evolution.

Biomolecule screening for efficient attachment of biofunctionalized microparticles to the zona pellucida of mammalian oocytes and embryos.

Science.gov (United States)

Novo, Sergio; Ibáñez, Elena; Barrios, Leonardo; Castell, Onofre; Nogués, Carme

2013-10-01

Individual tagging of oocytes and embryos through the attachment of micrometer-sized polysilicon barcodes to their zona pellucida (ZP) is a promising approach to ensure their correct identification and traceability in human assisted reproduction and in animal production programs. To provide barcodes with the capacity of binding to the ZP, they must be first biofunctionalized with a biomolecule capable of binding to the ZP of both oocytes and embryos. The aim of this work was to select, among an anti-ZP2 antibody and the two lectins wheat germ agglutinin (WGA) and phytohemagglutinin-L, the most optimal biomolecule for the eventual biofunctionalization of barcodes, using mouse oocytes and embryos and commercially available microspheres as a model. Despite the anti-ZP2 antibody showed the highest number of binding sites onto the ZP surface, as determined by field emission scanning electron microscopy, the binding of anti-ZP2-biofunctionalized microspheres to the ZP of cultured oocytes and embryos was less robust and less stable than the binding of lectin-biofunctionalized ones. WGA proved to be, among the three candidates tested, the most appropriate biomolecule to biofunctionalize microparticles with the aim to attach them to the ZP of both oocytes and embryos and to maintain them attached through oocyte activation (zona reaction) and in vitro culture up to the blastocyst stage. As saccharides recognized by WGA are highly abundant in the ZP of most mammalian species, WGA-biofuncionalized microparticles would be able to attach to the ZP of oocytes/embryos of species other than the mouse, such as humans and farm animals.

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

Energy Technology Data Exchange (ETDEWEB)

Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2015-04-01

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

International Nuclear Information System (INIS)

Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

2015-01-01

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

Cold storage of peaches cv. Aurora grown in the Zona da Mata Mineira, Minas Gerais State, Brazil

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Danielle Fabíola Pereira Silva

2013-12-01

Full Text Available This study aimed to evaluate the postharvest behavior of peach cv. Aurora 1 harvested in the Zona da Mata region of Minas Gerais in two ripening stages and kept under different storage temperatures. Fruits on mid-ripe and fully ripe stages were stored at three temperatures: 5.6 ± 1.57 °C and 72.8 ± 3.8% RH; 10.4 ± 0.5 °C and 95.8 ± 5.5% RH; 21.04 ± 1.63 °C and 96.9 ± 2.6% RH up to 28 storage days (SD . During storage, fruits stored at 21.04 ± 1.63 °C were evaluated every two days until 8 SD, and every four days for fruits stored at other temperatures. The harvest day was assigned as day zero. The variables evaluated were CO2 production, color of the pericarp and pulp, fresh mass loss, flesh firmness, total soluble solids, titratable acidity, contents of ascorbic acid and carotenoids. The fresh mass loss increased during storage, peaking at 5.6 °C. The reduction in ascorbic acid content was higher in fully ripe fruits at all temperatures. Mid-ripe fruits reached the end of the storage period with better quality. The temperature of 10.4 °C was the most efficient in keeping postharvest quality of peach cv. Aurora 1 harvested in the Zona da Mata region.

Incidencia de las zonas rurales sobre las posibles tipologías de turismo rural: el caso de Andalucía

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Mercedes Jiménez García

2014-01-01

Full Text Available España es un país tradicionalmente turístico, destacando Andalucía en este sector. El turismo rural se configura como una tipología turística con fuerte potencial de crecimiento e impacto sobre el desarrollo territorial. No obstante, si este turismo es el que se desarrolla en el espacio rural y en Andalucía conviven tres tipos de zonas rurales, ¿existen tres tipos de turismo rural con incidencia diferente sobre el desarrollo territorial? Para responder a este interrogante, desarrollado en el apartado introductorio, en un segundo epígrafe se analiza la relación entre las zonas rurales andaluzas y su oferta turística, en el tercero se valora la influencia de los tipos de turismo rural andaluz sobre el desarrollo territorial, centrándose, en el cuarto, en zonas rurales que no siguen el patrón identificado y en sus políticas de desarrollo. Finalmente, en base a todo lo anterior, se concluye con una respuesta afirmativa a la cuestión inicial.

Seismic monitoring at the geothermal zone of Acoculco, Pue., Mexico; Monitoreo sismico en la zona geotermica de Acoculco, Pue., Mexico

Energy Technology Data Exchange (ETDEWEB)

Lermo, Javier; Antayhua, Yanet; Bernal, Isabel [Universidad Nacional Autonoma de Mexico (UNAM), Instituto de Ingenieria Mexico, D.F. (Mexico); Venegas, Saul; Arredondo, Jesus [Comision Federal de Electricidad, Gerencia de Proyectos Geotermoelectricos, Morelia, Michoacan (Mexico)]. E-mail: jles@pumas.iingen.unam.mx

2009-01-15

Results are presented of a research project to study seismic activity in the Acoculco geothermal zone, Puebla, Mexico. Geological and geophysical information was collected for the zone and a seismic network composed of seven digital seismographs was installed over four months (August-November 2004). Of the 30 regional earthquakes located by the National Seismological Service, 14 were at the subduction zone, 7 in the intra-plate zone, 6 of cortical type were in the Mexican Volcanic Belt, and 3 had deep origins in the Veracruz and Chiapas regions. Although there were no local earthquakes, probably due to the short monitoring span or lack of currently active zones, velocity models were defined near the springs of Los Azufres and Alcaparrosa, with lineal arrangements of wide-band seismic stations (SPAC) and strata identified in the exploratory well EAC-1, drilled by the Comision Federal de Electricidad. By using the registers of regional earthquakes, the site-effects were estimated on the six temporary seismic stations, whose empirical transfer functions were used to validate a velocities model proposed for the endhoreic basin. The proposed velocity models, both for the endhoreic basin and outside it, enhance the previous interpretations. They confirm the geo-electrical model proposed for the zone is adequate and they provide dynamic conditions for the model, such as propagation velocities of the P and S waves and densities and attenuation. [Spanish] Se presentan los resultados de un proyecto de investigacion para estudiar la actividad sismica de la zona geotermica de Acoculco, Puebla, Mexico. Con este fin se recopilo informacion geologica y geofisica de la zona y se instalo durante cuatro meses (de agosto a noviembre de 2004) una red sismica conformada por siete sismografos digitales. Se registraron 30 sismos regionales que fueron localizados por el Servicio Sismologico Nacional en la zona de subduccion (14), en la zona de intraplaca (7), de tipo cortical del Eje

Loss of the zona pellucida-binding protein 2 (Zpbp2) gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion.

Science.gov (United States)

Kanagaratham, Cynthia; Chiwara, Victoria; Ho, Bianca; Moussette, Sanny; Youssef, Mina; Venuto, David; Jeannotte, Lucie; Bourque, Guillaume; de Sanctis, Juan Bautista; Radzioch, Danuta; Naumova, Anna K

2018-04-01

The human chromosomal region 17q12-q21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic interval that includes several protein-coding genes. Here, we tested the hypothesis that the zona pellucida-binding protein 2 (ZPBP2) gene residing in this region contributes to asthma pathogenesis using a mouse model. We tested the lung phenotypes of knock-out (KO) mice that carry a deletion of the Zpbp2 gene. The deletion attenuated airway hypersensitivity (AHR) in female, but not male, mice in the absence of allergic sensitization. Analysis of the lipid profiles of their lungs showed that female, but not male, KO mice had significantly lower levels of sphingosine-1-phosphate (S1P), very long-chain ceramides (VLCCs), and higher levels of long-chain ceramides compared to wild-type controls. Furthermore, in females, lung resistance following methacholine challenge correlated with lung S1P levels (Pearson correlation coefficient 0.57) suggesting a link between reduced AHR in KO females, Zpbp2 deletion, and S1P level regulation. In livers, spleens and blood plasma, however, VLCC, S1P, and sphingosine levels were reduced in both KO females and males. We also find that the Zpbp2 deletion was associated with gain of methylation in the adjacent DNA regions. Thus, we demonstrate that the mouse ortholog of ZPBP2 has a role in controlling AHR in female mice. Our data also suggest that Zpbp2 may act through regulation of ceramide metabolism. These findings highlight the importance of phospholipid metabolism for sexual dimorphism in AHR.

PP2A contributes to endothelial death in high glucose: inhibition by benfotiamine.

Science.gov (United States)

Du, Y; Kowluru, A; Kern, T S

2010-12-01

Endothelial death is critical in diabetic vascular diseases, but regulating factors have been only partially elucidated. Phosphatases play important regulatory roles in cell metabolism, but have not previously been implicated in hyperglycemia-induced cell death. We investigated the role of the phosphatase, type 2A protein phosphatase (PP2A), in hyperglycemia-induced changes in signaling and death in bovine aortic endothelial cells (BAEC). We explored also the influence of benfotiamine on this phosphatase. Activation of PP2A was assessed in BAEC by the extent of methylation and measurement of activity, and the enzyme was inhibited using selective pharmacological (okadaic acid, sodium fostriecin) and molecular (small interfering RNA) approaches. BAECs cultured in 30 mM glucose significantly increased PP2A methylation and activity, and PP2A inhibitors blocked these abnormalities. PP2A activity was increased also in aorta and retina from diabetic rats. NF-κB activity and cell death in BAEC were significantly increased in 30 mM glucose and inhibited by PP2A inhibition. NF-κB played a role in the hyperglycemia-induced death of BAEC, since blocking its translocation with SN50 also inhibited cell death. Inhibition of PP2A blocked the hyperglycemia-induced dephosphorylation of NF-κB and Bad, thus favoring cell survival. Incubation of benfotiamine with BAEC inhibited the high glucose-induced activation of PP2A and NF-κB and cell death, as well as several other metabolic defects, which likewise were inhibited by inhibitors of PP2A. Activation of PP2A contributes to endothelial cell death in high glucose, and beneficial actions of benfotiamine are due, at least in part, to inhibition of PP2A activation.

Corrosion Inhibition by Sodium Gluconate-Zn2+-DTPMP System

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P. Manjula

2009-01-01

Full Text Available The inhibition efficiency of a phosphonic acid, Diethylene Triamine Pentamethylene Phosphonic acid (DTPMP in controlling corrosion of carbon steel immersed in an aqueous solution containing 60 ppm of Cl- has been evaluated by weight loss method in the absence and presence of Zn2+. The formulation consisting of DTPMP and Zn2+ has excellent inhibition efficiency (IE. A synergistic effect is noticed between Zn2+ and DTPMP. Addition of sodium gluconate (SG enhances the IE of Zn2+ and DTPMP system. The DTPMP-Zn2+-SG system function as a mixed inhibitor as revealed by polarization study. AC impedance spectrum, optical and atomic force micrographs reveal the formation of a protective film on the metal surface. FTIR spectra reveal that the protective film consists of Fe2+-DTPMP complex, Fe2+-SG complex and Zn(OH2.

Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells

Energy Technology Data Exchange (ETDEWEB)

Conde, Patricia; Acosta-Saavedra, Leonor C.; Calderon-Aranda, Emma S. [Centro de Investigacion y de Estudios Avanzados, CINVESTAV, Seccion Toxicologia, P.O. Box 14-740, Mexico, D.F. (Mexico); Goytia-Acevedo, Raquel C. [Universidad Juarez del Estado de Durango, Facultad de Medicina, Gomez Palacio, Durango (Mexico)

2007-04-15

A proposed mechanism for the As-induced inhibition of cell proliferation is the inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA expression or on the ERK pathway in activated-T cells have not yet been described. We examined the effect of arsenite on IL-2 mRNA expression, cell activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1 and 10 {mu}M) decreased IL-2 mRNA expression, IL-2 secretion and cell proliferation. Arsenite (10 {mu}M) strongly inhibited ERK-phosphorylation. However, the partial inhibition (50%) of IL-2 mRNA produced by 1 {mu}M, consistent with the effects on IL-2 secretion and cell proliferation, could not be explained by the inhibition of ERK-phosphorylation, which was not affected at this concentration. The inhibition of IL-2 mRNA expression caused by 1 {mu}M could be associated to effects on pathways located downstream or parallel to ERK. Arsenite also decreased early activation (surface CD69{sup +} expression) in both CD4{sup +} and CD8{sup +}, and decreased total CD8{sup +} count without significantly affecting CD4{sup +}, supporting that the cellular immune response mediated by cytotoxic T cells is an arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA levels and T-cell activation and proliferation. However, further studies on the effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are needed. (orig.)

EMERGÊNCIA DOS "CONDOMÍNIOS-CLUBE" NA ZONA SUL DE NATAL/RN, BRASIL

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Felipe Fernandes de Araújo

2012-01-01

Full Text Available Este documento tiene como objetivo discutir el surgimiento de una nueva tipología residencial que se ha extendido en el sur de Natal / RN, los condominios llamado Club. Su principal característica es la apelación a los artículos de ocio más diversos, que son utilizados por los empresarios urbanos como una forma de crear un nuevo estilo de vida y un nuevo producto que se vende. La base teórica de este trabajo se basa en el enfoque heterodoxo de la coordinación espacial realizada por Pedro Abramo. Esta perspectiva considera el espacio urbano como un conjunto de inventario de viviendas que son ofrecidas por los empresarios urbanos. En general, el orden urbano y el ambiente residencial es incierto, porque sufren cambios derivados de la aparición de las innovaciones de espacio causadas por empresarios urbanos en busca de beneficios extraordinarios. En el caso de la zona sur de Natal, la construcción de carreteras principales que conectan esta zona de la ciudad al vecino municipio de Parnamirim, que ha sido el blanco de la abundancia del mercado inmobiliario de Natal. El ciclo de vida de los inventarios residenciales de la Zona Sur de Natal ha cambiado con el tiempo, desde el principio de la vivienda en grandes alojamientos para la producción de proyectos verticais. En la actualidad, un fenómeno nuevo que se plantea es la propagación de una nueva clasificación, los condominios club. Al ser un caso reciente en que los proyectos se encuentran todavía en fase de lanzamiento o de la construcción, el estudio se llevará a cabo mediante el análisis de marketing utilizadas por los empresarios urbanos para atraer a los consumidores a través de panfletos y folletos.

Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

International Nuclear Information System (INIS)

Forward, Nicholas A.; Conrad, David M.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Furlong, Suzanne J.; Lin, Tong-Jun; Hoskin, David W.

2011-01-01

Highlights: → Curcumin inhibits CD4 + T-lymphocyte proliferation. → Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4 + T-lymphocytes. → Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. → IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4 + T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 (α chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca 2+ release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4 + CD25 + regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

Metas de socialización maternas: relación con edad, formación académica y zona habitacional

OpenAIRE

Jorge Mario Jaramillo; Laura Pérez; Karen Alexandra González

2013-01-01

En este artículo analizamos como la zona de vivienda (rural/urbana), el nivel de formación académica y la edad de las madres se relacionan con sus metas de socialización. Por medio de una entrevista individual estructurada pedimos a 163 madres de la ciudad de Bogotá y varios municipios de la zona rural cundiboyacense hacer una estimación del valor atribuido a distintas metas en la socialización de sus hijos e hijas de edades entre 3 y 4 años y medio. Con esto buscábamos identificar los valore...

Condiciones de Drenaje de Suelos Orgánicos en la Zona de Aragón, Santa Rosa de Osos (Antioouia

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Gómez Juan Mauricio

1985-12-01

Full Text Available Se puede decir que la zona de Santa Rosa de Osos, Yarumal y Entrerrios presenta un problema de drenaje de suelos a los cuales se le ha tratado de dar la misma solución con zanjas poco profundas y espaciadas. Los suelos de toda esta zona son en su gran mayoría suelos desarrollados a partir de cenizas volcánicas depositados sobre coluviones y aluviones heterogéneos moderadamente profundos, limitados en algunas áreas por gravillas, cascajos, piedras en el perfil y por capas endurecidas de óxidos de hierro.

Verruga y Uta en el valle de Huaillacayan (Dpto. de Ancash.: I. Determinación de los límites altitudinales de la zona endémica y de la incidencia de ambas enfermedades

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Arístides Herrer

1957-12-01

Full Text Available Se ofrece los resultados de observaciones epidemiológicas acerca de la enfermedad de Carrión (verruga peruana y la leishmaniasis tegumentaria (uta realizadas en el valle de Huaillacayán (10º18' de latitud Sur, tendientes a determinar los límites altitudinales de las respectivas zonas endémcias y la incidencia de ambas enfermedades en relación con la altura sobre el nivel del mar, obteniendo las siguientes conclusiones: 1. La zona endémica de la uta está comprendida entre los 900 y 3,000 metros de altura sobre el nivel del mar. También para la verruga el límite superior de la respectiva zona endémica está alrededor de los 3,000 metros. En este caso el límite inferior no ha sido determinado, debido a que la región comprendida entre el nivel del mar hasta los 780 metros de altura ha sido objeto de periódicas aplicaciones del insecticida DDT desde varios años atrás. No obstante, cabe suponer que en el valle de Huaillacayán la zona verrucógena descienda más que la utógena. 2. La incidencia tanto de la verruga como de la uta parece estar determinada fundamentalmente por la altura de las localidades sobre el nivel del mar. En la verruga la máxima incidencia se observa entre los 900 y 1,800 metros de altitud, y en la uta entre los 1,800 y 2,700 metros. 3. En el valle de Huaillacayán tanto la zona verrucógena como la utógena descienden más que en el valle del Rímac, que se encuentra a grado y medio de latitud al sur del de Huaillacayán.

The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model

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Paiboon Jungsuwadee

2012-08-01

Full Text Available MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone marrow derived dendritic cells (DC and OVA_323-339-specific Th2 cells were cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to the co-culturing of the two cell types in the presence of an OVA_323-339 peptide and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL-4, IL-5 and IFNγ production and inhibited Th2 cell proliferation in the DC-Th2 co-culturing system in the presence of the OVA_323-339 peptide. Similar results were obtained using the CD3/CD28 cell-activation system; the addition of MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25 expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC and suppressing Th2 cell proliferation and activation.

Medición de la inflación en la zona euro

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Rodríguez Ruíz, Julián.

2003-01-01

Full Text Available El objeto de este documento consiste en analizar si los movimientos en la “inflación medida” recogen adecuadamente el fenómeno inflacionario para algunos países de la zona euro. Para ello se utiliza la metodología propuesta por Quah y Valhey basada en sistemas de Vectores Autorregresivos Estructurales. La aproximación es consistente con la interpretación de la curva de Phillips a largo plazo.

Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

Science.gov (United States)

Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A G

2016-01-01

This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

Directory of Open Access Journals (Sweden)

Sanjay Kalra

2016-01-01

Full Text Available This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2 inhibition: Calorie restriction mimicry (CRM and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

Límites urbanos de una zona típica: La Serena

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Fernando Glasinovic Duhalde

2013-05-01

Este trabajo, que no es la historia de una acción terminada sino más bien la relación de su inicio, revisa aspectos relevantes a considerar en la delimitación de la Zona Típica de la Ciudad, comenzando el análisis desde los aspectos del diseño de la ciudad, trascendentes y fundamentales, que son iniciadores de una identidad urbana que es depositaria de una particular arquitectura que es también sensible a esta estructura subyacente que habita en la memoria colectiva.

Geología de la extremidad oriental de la zona sudportuguesa

OpenAIRE

Simancas Cabrera, José Fernando

2013-01-01

Se ha efectuado un estudio de geología regional en la extremidad oriental de la zona Sudportuguesa estableciéndose nuevas unidades litoestratigráficas en los materiales del devonico superior y carbonífero inferior y en la cuenca del Viar. Se han estudiado los caracteres mineralógicos y geoquímicos del vulcanismo pretectónico del plutonismo sin-postectónico y del vulcanismo tardiherciano y se han establecido las deformaciones de plegamiento y la existencia de una notable cizalla frágil tardía ...

Synthesis and Antimycobacterial and Photosynthesis-Inhibiting Evaluation of 2-[(E-2-Substituted-ethenyl]-1,3-benzoxazoles

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Ales Imramovsky

2014-01-01

Full Text Available A series of twelve 2-[(E-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. 2-[(E-2-(4-Methoxyphenylethenyl]-1,3-benzoxazole, 2-[(E-2-(2,3-dihydro-1-benzofuran-5-ylethenyl]-1,3-benzoxazole and 2-{(E-2-[4-(methylsulfanylphenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E-2-(2-methoxyphenylethenyl]-1,3-benzoxazole was IC50 = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed.

Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.

Science.gov (United States)

Kang, Dong Young; S P, Nipin; Darvin, Pramod; Joung, Youn Hee; Byun, Hyo Joo; Do, Chang Hee; Park, Kyung Do; Park, Mi Na; Cho, Kwang Hyun; Yang, Young Mok

2017-07-03

Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.

PEMETAAN ZONA POTENSI PENANGKAPAN IKAN CAKALANG PERIODE APRIL-JUNI DI TELUK BONE DENGAN TEKNOLOGI REMOTE SENSING

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Mukti Zainuddin

2016-03-01

Full Text Available Satelit penginderaan jauh dapat memberikan informasi sistematis tentang kondisi oseanografi. Penelitian ini bertujuan memetakan zona potensial penangkapan ikan (ZPPI cakalang di Teluk Bone selama April-Juni 2012 menggunakan citra suhu permukaan laut (SPL dan klorofil-a yang dikombinasikan dengan data penangkapan pole and line.  ZPPI dipetakan menggunakan teknik sistem informasi geografis yang dikonstruksi dari hasil analisis fungsi distribusi kumulatif empiris dan generalized additive model (GAM. Hasil penelitian menunjukkan bahwa selama bulan April-Juni di Teluk Bone, ZPPI cenderung berada pada area 120.5-121.5° BT dan 3.5-5° LS. Lokasi dengan nilai Catch per unit effort (CPUE yang tinggi tersebut diindikasikan dengan kondisi SPL dan konsentrasi klorofil-a masing-masing antara 28.75-31.5° C dan antara 0.10 dan 0.2 mg m-3.  Kombinasi nilai preferensi faktor oseanografis tersebut diduga kuat merefleksikan kondisi kelimpahan makanan yang cukup tinggi dimana zona tersebut pada gilirannya menjadi daerah tempat berkumpulnya gerombolan ikan cakalang dan menjadi zona target bagi penangkapan pole and line di Teluk Bone.   Satellite remote sensing provides systematically important information on oceanographic conditions. Sea surface temperature (SST and sea surface chlorophyll-a concentration (Chl-a derived from Aqua/ Moderate Resolution Imaging Spectroradiometer (MODIS data together with skipjack catch data during April-June 2012 were used to map potential fishing zones for skipjack tuna in the Bone Bay.  Geographic information system was then employed to map out of the potential fishing zones generated by non-linear model (Generalized Additive Model/GAM and the empirical cumulative distribution function (ECDF analyses.  Results indicated that the highest catch per unit efforts (CPUE mostly occurred in areas of 120.5-121.5° E dan 3.5-5° S. These areas were significantly associated with SST and chlorophyll-a concentration ranged from 28.75- 31

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

Science.gov (United States)

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

3-(2-Alkylsulfanyl-6-benzothiazolylaminomethyl-2-benzoxazolethiones - Synthesis and Photosynthesis-Inhibiting Activity in Spinach Chloropasts

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Dusan Loos

1999-03-01

Full Text Available The synthesis and photosynthesis-inhibiting activity of 14 new 3-(2-alkylsulfanyl-6-benzothiazolylaminomethyl-2-benzoxazolethiones are reported. The new compounds were prepared by the reaction of 2-alkylsulfanyl-6-aminobenzothiazoles with 3-hydroxymethyl-2-benzoxazolethione. The structures of the compounds were verified by 1H NMR spectra. The compounds inhibit photosynthetic electron transport in spinach chloroplasts. The photosynthetic activity was found to depend on the calculated lipophilicity of the new compounds. Some structure characteristics and quantum chemical parameters were calculated by AM1 method.

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin

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Bo Ahrén

2008-04-01

Full Text Available Bo AhrénDepartment of Clinical Sciences, Division of Medicine, Lund University, Lund, SwedenAbstract: Inhibition of dipeptidyl peptidase-4 (DPP-4 as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1. Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis and sitagliptin (JanuviaR, Merck. These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1c levels by 0.65%–1.1% (baseline HbA1c 7.2–8.7% in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1c was reduced by this combination by 2.1% (baseline HbA1c 8.8% after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.Keywords: DPP-4 inhibition, sitagliptin, vildagliptin, metformin, type 2 diabetes

Método Expedito para a Análise de Qualidade Ambiental em Zonas Ripárias Urbanas

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Ricardo Siloto da Silva

2012-12-01

Full Text Available Desde o estabelecimento das primeiras cidades, as áreas marginais aos rios são amplamente incorporadas na produção do espaço urbano. Visando contribuir para a reversão dos impactos da urbanização sobre estas áreas,  o trabalho apresenta  um método expedito para análise da qualidade ambiental nas zonas ripárias urbanas. Foi definido um conjunto de variáveis interdisciplinares e critérios de análise, e foram coletados dados em córregos localizados em cidades distintas. Como resultados parciais, o estudo identificou dificuldades quanto ao procedimento de coleta de dados  o que conduziu a alteração dos critérios de análise para o sistema canal fluvial-zona ripária.

Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

Energy Technology Data Exchange (ETDEWEB)

Forward, Nicholas A.; Conrad, David M. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Power Coombs, Melanie R.; Doucette, Carolyn D. [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Furlong, Suzanne J. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Lin, Tong-Jun [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

2011-04-22

Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

LAS INVERSIONES TÉRMICAS Y LA CONTAMINACIÓN ATMOSFÉRICA EN LA ZONA METROPOLITANA DE GUADALAJARA (MÉXICO

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M. García

2012-01-01

Full Text Available El objetivo de este trabajo es analizar el comportamiento de las inversiones tér - micas y contaminantes atmosféricos en la Zona Metropolitana de Guadalajara (ZMG durante el periodo 2005-2007. Se analizó la información de las inver - siones térmicas (estación CNA colomos y concentraciones de los contaminan - tes: monóxido de carbono, bióxido de nitrógeno, ozono, bióxido de azufre y partículas menores a 10 micras de las ocho estaciones de la Red de Monitoreo Atmosférico del Gobierno de Jalisco. Los resultados mostraron relación signi - ficativa entre los días con inversión térmica de gran espesor y duración con la acumulación de contaminantes, lo cual provoca que se incrementen los índices de contaminación en la zona. Los meses con presencia importante de inversiones térmicas y contaminación elevada ocurrieron durante las estaciones de invierno y primavera (noviembre-mayo. Una conclusión relevante es que las inversiones térmicas fuertes han sido factor en elevados índices de contaminación en la ZMG. Palabras clave: Inversiones térmicas, contaminantes atmosféricos, Zona Metropolitana de Guadalajara

Morbidades e qualidade de vida de idosos com diabetes mellitus residentes nas zonas rural e urbana Morbilidades y calidad de vida de ancianos con diabetes mellitus residentes en zonas rurales y urbanas Morbidity and quality of life of elderly individuals with diabetes mellitus living in urban and rural areas

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Érica Aparecida dos Santos

2013-04-01

Full Text Available Este estudo objetivou descrever as variáveis sociodemográficas e comparar as morbidades e a qualidade de vida (QV dos idosos com diabetes mellitus (DM residentes nas zonas urbana e rural. A amostra foi composta de 271 idosos da zona urbana e 104 da rural que autorreferiram DM. Utilizou-se análise descritiva e, na comparação das localidades, realizou-se ajuste para a idade por meio de regressão logística e linear múltipla (p Se objetivó describir las variables sociodemográficas y comparar morbilidades y calidad de vida (QV de ancianos con diabetes mellitus (DM residentes en zonas urbanas y rurales. Muestra compuesta por 271 ancianos de zona urbana y 104 de zona rural que autorrefirieron padecer DM. Se utilizó análisis descriptivo y, en la comparación de localidades, se efectuó ajuste etario mediante regresión logística y lineal múltiple (pThis study aimed to describe the socio-demographic variables and to compare the morbidities and the quality of life (QoL of elderly individuals with diabetes mellitus (DM residing in urban and rural areas. The sample consisted of 271 elderly individuals from urban areas and 104 from rural areas with self-reported DM. A descriptive analysis was used, and in the location comparison, an age adjustment was employed through linear and logistic multiple regression models (p<0.05. The elderly individuals from the rural area were younger, more educated, earned a higher income and were more often married in relation to the urban residents. Furthermore, the rural residents presented a higher QoL score in the physical and social relationships domains and in the autonomy, past, present and future activities, and intimacy facets compared to the urban residents. The elderly individuals residing in the urban area displayed a larger number of verified comorbidities. The elderly DM patients residing in the rural area generally presented better health conditions than those who lived in the urban area.

Sexualidades marginalizadas: un acercamiento a la zona de tolerancia en Cali, 1960-1970

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Diana Carolina Gutiérrez Ramírez

2016-01-01

Full Text Available Interesa al presente artículo la zona de tolerancia como receptáculo de sexualidades marginalizadas en el que pululan prácticas, sujetos e imaginarios anormales, inmorales y transgresores a la norma sexual en la ciudad de Cali, entre 1960 y 1970. A partir de lo anterior se posibilitará un acercamiento al Estado como ejecutor de poder y a la zona como un lugar donde habita, vive y existe la diferencia. Teniendo presentes las dinámicas típicas de este espacio, se prestará atención a la forma como este lugar se convirtió en el sitio idóneo de venta y circulación del mercado pornográfico de la época. Esto con el fin de comprender el surgimiento y popularización de la narrativa pornográfica del escritor caleño Hernán Hoyos. En ese momento se realizará una lectura sobre los imaginarios y lugares comunes que se configuran en la obra de este autor. Por último, se intentará comprender al libro pornográfico, y las realidades que allí se tejen, como elemento configurador de la cultura popular.

Estudio comparativo de la frecuencia de Blastocystis hominis en niños en edad preescolar de una zona urbana y una rural de la ciudad de Cartagena de Indias y su relación con las manifestaciones clínicas y factores de riesgo

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Mavianis Pinilla Pérez

2015-01-01

Full Text Available Introducción: las parasitosis intestinales son infecciones comunes a nivel mundial y de mayor prevalencia en las comunidades empobrecidas de países en desarrollo. A finales de los ochenta el Blastocystis hominis no era reportado rutinariamente, representando solo un problema de diagnóstico diferencial; pero en los noventa mediante un oportuno diagnóstico aumenta su prevalencia de 1,5 a 10% en los países desarrollados y de 30 a 50 % en países en desarrollo. Objetivo: comparar la frecuencia de Blastocystis hominis en niños de preescolar de una zona urbana (Crespo y una rural (Boquilla de Cartagena Bolívar y su relación con las manifestaciones clínicas, factores de riesgo. Materiales y métodos: se analizaron mediante la técnica de coprológico seriado, 286 muestras de materia fecal de niños de 1 a 5 años que procedían de una zona urbana y una zona rural de la ciudad de Cartagena de indias. Resultados: se encontraron parásitos en el 38,5% (55/143 de los niños de la zona urbana y el 79% (113/143 de la zona rural. Se encontró asociación entre la presencia de parásitos con la procedencia de los niños evaluados (X2= 48,53; p<0,0001. Se encontró una frecuencia de 51,1% de B. hominis en la zona urbana y 44,8% en la zona rural. Conclusiones: la falta de seguimiento y control de los casos problema sugiere la necesidad de formular e implementar medidas orientadas a mejorar la calidad de vida en las zonas estudiadas.

Violencia basada en género en zonas urbanas y urbano-marginales de Lima y Callao, 2007 - 2010

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Pedro Mascaro-Sánchez

2012-04-01

Full Text Available Objetivos: Determinar y comparar las características de la violencia en pobladores de zonas urbanas y urbano-marginales. Diseño: Estudio epidemiológico descriptivo. Institución: Escuela de Obstetricia, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Mujeres de Lima y Callao. Intervenciones: Entre los años 2007 y 2010, se aplicó una entrevista estructurada a 3 971 mujeres de zonas urbanas y urbano-marginales de Lima y Callao. Se incluyó mujeres residentes de la zona, excluyéndose aquellas con problemas psicológicos evidentes y problemas del habla. Los datos fueron analizados con estadísticas descriptivas y con el estadístico chi cuadrado, significativo a un nivel p<0,05. Principales medidas de resultados: Violencia física. Resultados: De las entrevistadas, 39% tenía entre 20 y 24 años de edad. El 47% identificó violencia física, siendo similar en zonas urbanas y urbano-marginales. Los empujones y bofetadas fueron la forma más frecuente de violencia en ambas áreas. Con respecto al estudio de la violencia psicológica, fueron más frecuentes la utilización de gritos y celos por posesividad, también en ambas áreas. El gasto de la pareja sin la consulta fue ligeramente mayor para el área urbano marginal (49% que para el área urbana (42%. El intento de tener relaciones sexuales contra su voluntad fue el tipo de violencia más frecuente (37%, más en el área urbana (41% que en el área urbano marginal (34%. Conclusiones: Se evidenció episodios de violencia física, psicológica, económica y sexual similares para el área urbana y el área urbano-marginal, siendo la violencia sexual más frecuente en el área urbana.

Costo energético de muros y techos utilizados en la zona sur de Tamaulipas

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Mireya Alicia Rosas Lusett

2015-01-01

Full Text Available El presente trabajo muestra los procedimientos y resultados obtenidos del análisis de la energía trasmitida en techos y muros de las viviendas seleccionadas de la zona sur del estado de Tamaulipas, una de las cinco áreas establecidas dentro del proyecto “Desarrollo y validación de una metodología para estimar los impactos en el ahorro de energía por el uso de sistemas pasivo-constructivos en la edificación para diferentes climas de México”. Este proyecto fue financiado por la Convocatoria S0019-2009-01 del Fondo Sectorial de Sustentabilidad Energética SENER-CONACYT con registro Nº 118665, cuyo objetivo en su tercera etapa de ejecución, consistió en hacer uso de la herramienta Ener-Habitat, la cual fue desarrollada durante la segunda fase del proyecto. Con dicho programa de cálculo se determinaron los gastos de energía, comparativa de cuatro sistemas constructivos para muros y tres sistemas constructivos para losas utilizadas en la zona sur de Tamaulipas. Con la información obtenida y mediante el uso de la metodología desarrollada para estimar los impactos en el ahorro de energía, se evaluó el costo energético de cada uno de los sistemas constructivos. Con los resultados obtenidos se pudo determinar cuál era el muro y techo de menor gasto de energía para la zona de estudio. Adicionalmente se realizó un estudio de la influencia de la absortancia solar de la superficie exterior de los muros, cuyos resultados darán la pauta para diseñar una vivienda que pretende sea adecuada y cómoda al clima cálido húmedo que prevalece en el área.

Desnutrición y desarrollo cognitivo en infantes de zonas rurales marginadas de México

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María del Refugio Carrasco Quintero

2016-07-01

Conclusión: Aunque la desnutrición aguda (identificada por el peso ya no es un problema en las zonas rurales de México, la desnutrición crónica (expresada como baja estatura sigue siendo frecuente y se relaciona con alteraciones en el desarrollo mental de la población infantil.

Zona Incerta: o ARG como meio de construção colaborativa de conteúdo

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Gabriel Costa Correia

2011-05-01

Full Text Available O presente artigo discorrerá sobre um estudo de caso realizado sobre o Alternate Reality Game (ARG Zona Incerta, realizado por membros da equipe da revista Superinteressante, publicação da Editora Abril, como estratégia de marketing alternativa para o produto Guaraná Antarctica, da empresa de bebidas AMBEV.

Inhibition of oxidative phosphorylation in ascites tumor mitochondria and cells by intramitochondrial Ca2+.

Science.gov (United States)

Villalobo, A; Lehninger, A L

1980-03-25

Accumulation of Ca2+ (+ phosphate) by respiring mitochondria from Ehrlich ascites or AS30-D hepatoma tumor cells inhibits subsequent phosphorylating respiration in response to ADP. The respiratory chain is still functional since a proton-conducting uncoupler produces a normal stimulation of electron transport. The inhibition of phosphorylating respiration is caused by intramitochondrial Ca2+ (+ phosphate). ATP + Mg2+ together, but not singly, prevents the inhibitory action of Ca2+. Neither AMP, GTP, GDP, nor any other nucleoside 5'-triphosphate or 5'-diphosphate could replace ATP in this effect. Phosphorylating respiration on NAD(NADP)-linked substrates was much more susceptible to the inhibitory effect of intramitochondrial Ca2+ than succinate-linked respiration. Significant inhibition of oxidative phosphorylation is given by the endogenous Ca2+ present in freshly isolated tumor mitochondria. The phosphorylating respiration of permeabilized Ehrlich ascites tumor cells is also inhibited by Ca2+ accumulated by the mitochondria in situ. Possible causes of the Ca2+-induced inhibition of oxidative phosphorylation are considered.

Panel of monoclonal antibodies to sperm surface proteins as a tool for monitoring localization and identification of sperm-zona pellucida receptors

Czech Academy of Sciences Publication Activity Database

Zigo, Michal; Dorosh, Andriy; Pohlová, Alžběta; Jonáková, Věra; Šulc, Miroslav; Maňásková-Postlerová, Pavla

March, č. 359 (2015), s. 895-908 ISSN 0302-766X R&D Projects: GA ČR(CZ) GA14-05547S; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 ; RVO:61388971 Keywords : zona pellucida-binding receptors * monoclonal antibodies against sperm surface proteins * sperm surface proteins * RAB-2A * lactahedrin P47 Subject RIV: CE - Biochemistry Impact factor: 2.948, year: 2015

Avaliação de cultivares de alfafa na Zona da Mata de Minas Gerais Evaluation of alfalfa cultivars in the region of Zona da Mata, Minas Gerais

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Francisco José da Silva Lédo

2004-10-01

Full Text Available Realizou-se este trabalho com o objetivo de avaliar e selecionar cultivares de alfafa (Medicago sativa L. mais adaptadas às condições edafoclimáticas da Zona da Mata de Minas Gerais. O ensaio foi conduzido no campo experimental da Embrapa Gado de Leite, em Coronel Pacheco-MG, no delineamento experimental de blocos casualizados com duas repetições. Foram avaliadas 59 cultivares no período de 31/8/1999 a 10/12/2001, realizando-se 16 cortes de avaliação. Avaliaram-se a produção de matéria seca (PMS, altura da planta (AP, vigor (VG, porcentagem de floração (FLO, relação folha/caule (RFC, e incidência de doenças (ID e pragas (IP. Para PMS, AP, VG, FLO e ID, observaram-se diferenças significativas entre as cultivares. As cultivares P-30, Crioula C-1, Crioula C-3 e Crioula C-2 foram as que apresentaram maiores PMS (13,17; 13,13; 13,00 e 12,48 t/ha/ano, respectivamente. As cultivares apresentaram maior FLO (18,98% e AP (54,13 cm nos cortes realizados no período de verão, quando comparado com os de inverno (6,11% e 46,60 cm, respectivamente. Com base nos resultados obtidos, foram selecionadas as cultivares P-30, Crioula C-1, Crioula C-3 e Crioula C-2.The objective of this experiment was to evaluate and select the alfalfa cultivars (Medicago sativa L. best adapted to the climate and soil of Zona da Mata, in Minas Gerais, Brazil. The trial was carried out at Embrapa Gado de Leite, in the experiment station located in Coronel Pacheco, MG, using a randomized complete block design with two replications. Fifty-nine cultivars studied between Sept. 9, 1999 and Dec. 10, 2001 were submitted to 16 evaluating cuts. Dry matter production (DMP, plant height (PH, vigor (VG, flowering percent (FLO, leaf/stem ratio (RFC and disease (D and pests (P occurrence were observed. There were significant differences among cultivars regarding to DMP, PH, VG, FLO and D. Cultivars P-30, Crioula C-3 and Crioula C-2 showed the highest DMP (13,17; 13,13; 13,00 e 12

Las abejas de Porce familia colletidae (hymenoptera: apoidea notas y claves para los géneros presentes en la zona de influencia del embalse Porce ii.

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Smith Pardo Allan H.

1999-12-01

Full Text Available Se presentan claves taxonómicas a nivel de género para la identificación de las abejas colletidas de la zona de Influencia del Embalse Porce II (Porce, Antioquía, Colombia S.A. Adicionalmente se presentan algunas notas para los géneros de colletidos capturados durante el inventario de las abejas silvestres de la zona.

El Alabama en la Zona Algodonera de Armero

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Velasco Llanos Vicente

1939-10-01

Full Text Available El gusano cortador de la hoja del algodonero, comúnmente llamado Alabama por todos los plantadores de algodón de la región de Armero, ha merecido y seguirá mereciendo una especial atención, ya que constituye la plaga más importante de cuantas diezman los cultivos de algodón. Si bien es cierto que otros insectos como el gusano rosado colombiano de las cápsulas del algodonero (SacadodespyralisDyar (7; nuevo género y nueva especie, según W m. Schaus, y el pulgón (AphisgossypiiGlov. causan daños de consideración, ninguno de ellos ha mostrado, en esta zona, la enorme voracidad y por lo tanto la fuerza destructora del insecto que tratamos. El Alabama fue la causa de casi todos los fracasos que tuvieron los primeros cultivadores en algunas regiones del interior del país. En ese entonces no había facilidad para su control, como la hay ahora, y era muy común ver un cultivo devastado en pocos días por la plaga en mención, sin que hubiera manera de destruirla. El hecho indiscutible de haberse iniciado el cultivo del algodón en la región de Armero sobre bases técnicas, de haber recibido el apoyo irrestricto y entusiasta de los,gobiernos departamental y nacional, de crear entidades y centros de investigación al servicio de la economía del país, y de poseer vías accesibles a,los mercados de importancia, son las razones inmediatas del éxito rotundo y progresivo de la industria algodonera en esta zona. A pesar de todo esto, el Alabama se presentó desde el primer momento y ha continuado haciendo sus daños de cosecha en cosecha, obligando a,los cultivadores a equiparse con máquinas espolvoreadoras de diversos tipos y a usar los insecticidas aconsejados por la técnica que les dieron resultados positivos; yel insecto, que antes constituía un problema para el cultivo, pasó a ser solo objeto de una inversión en el presupuesto del cultivador.

A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

Science.gov (United States)

Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

2012-10-01

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species.

Science.gov (United States)

Yang, Ji Seon; Perveen, Shazia; Ha, Tae Joung; Kim, Seong Yun; Yoon, Shin Hee

2015-05-05

Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. However, effects of C3G on glutamate-induced [Zn(2+)]i increase and neuronal cell death remain unknown. We studied the effects of C3G on glutamate-induced [Zn(2+)]i increase and cell death in cultured rat hippocampal neurons from embryonic day 17 maternal Sprague-Dawley rats using digital imaging methods for Zn(2+), Ca(2+), reactive oxygen species (ROS), mitochondrial membrane potential and a MTT assay for cell survival. Treatment with glutamate (100 µM) for 7 min induces reproducible [Zn(2+)]i increase at 35 min interval in cultured rat hippocampal neurons. The intracellular Zn(2+)-chelator TPEN markedly blocked glutamate-induced [Zn(2+)]i increase, but the extracellular Zn(2+) chelator CaEDTA did not affect glutamate-induced [Zn(2+)]i increase. C3G inhibited the glutamate-induced [Zn(2+)]i response in a concentration-dependent manner (IC50 of 14.1 ± 1.1 µg/ml). C3G also significantly inhibited glutamate-induced [Ca(2+)]i increase. Two antioxidants such as Trolox and DTT significantly inhibited the glutamate-induced [Zn(2+)]i response, but they did not affect the [Ca(2+)]i responses. C3G blocked glutamate-induced formation of ROS. Trolox and DTT also inhibited the formation of ROS. C3G significantly inhibited glutamate-induced mitochondrial depolarization. However, TPEN, Trolox and DTT did not affect the mitochondrial depolarization. C3G, Trolox and DTT attenuated glutamate-induced neuronal cell death in cultured rat hippocampal neurons, respectively. Taken together, all these results suggest that cyanidin-3-glucoside inhibits glutamate-induced [Zn(2+)]i increase through a release of Zn(2+) from intracellular sources in cultured rat hippocampal neurons by inhibiting Ca(2+)-induced mitochondrial depolarization and formation of ROS, which is involved in neuroprotection against glutamate-induced cell death. Copyright © 2015 Elsevier B.V. All rights reserved.

Disponibilidad de Ca2+, Mg2+ y K+ en función de las propiedades del suelo, zona cafetera central de Colombia

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Luz Adriana Lince Salazar

2015-03-01

Full Text Available La nutrición mineral se da a partir de los elementos que se encuentran en forma disponible en la solución del suelo, la cual se abastece principalmentede la fase de cambio iónico. Con el objetivo de determinar la disponibilidad de cationes en la solución del suelo y su relación con las propiedades edáficas, se realizó una investigación con suelos provenientes de cinco unidades cartográficas de la zona cafetera central de Colombia. Por cada unidad cartográfica se seleccionó un lote cafetero, en el que se tomaron muestras de suelo a diferentes profundidades y se analizaron las características físicas, químicas y mineralógicas, incluyendo la concentración de Ca2+, Mg2+ y K+ en la solución.En las cinco unidades el catión predominante fue Ca2+, seguido por Mg2+ y K+, y las concentraciones de éstos para la fase de cambio y la solución, enla mayoría fueron iguales en los primeros 30 cm de profundidad y diferentes entre unidades, de las cuales las unidades Catarina, Doscientos y Guamal,presentaron los valores más altos y Quindío y Chinchiná los más bajos, lo cual se relacionó con el material parental ya que las tres primeras provienende rocas máficas y ultramáficas y las dosúltimas de materiales de composición intermedia. Finalmente las concentraciones de Ca2+ en la solución se explicaron desde 36,97 % hasta 88,11 % por la fase de cambio, las de Mg2+ desde 32,23 % hasta 97,30 % y las de K+ desde 79,06 % hasta 94,68 %, mediante modelos lineales que incluyeron nutrientes del suelo y propiedades como CIC, pH y contenido de arcillas.

Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2 inhibitor.

Science.gov (United States)

Kalle, Arunasree M; Rizvi, Arshad

2011-01-01

Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. Here, we demonstrate that celecoxib increases the sensitivity of bacteria to the antibiotics ampicillin, kanamycin, chloramphenicol, and ciprofloxacin by accumulating the drugs inside the cell, thus reversing MDR in bacteria.

Análisis estructural a escala regional de la zona de fallas La Trocha

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Jesús A. Blanco-Moreno

2007-03-01

Full Text Available Se realiza un análisis estructural a escala regional de la zona de fallas La Trocha, a partir de la interpretación de un gran volumen de información geólogo–geofísica, la cual fue clasificada como: morfométrica, gravimétrica, geológica de superficie y del subsuelo. Se obtuvo el modelo digital del terreno (MDT, a partir de la digitalización de 24 cartas del Mapa Topográfico de la República de Cuba 1:50000, editado por el Instituto Cubano de Geodesia y Cartografía en 1977. El procesamiento del MDT permitió obtener los principales morfoalineamientos de la región. Se procesó la información obtenida del levantamiento gravimétrico de la Cuenca Central a escala 1:100000, elaborándose los mapas de anomalías de Bouguer, continuaciones analíticas ascendentes y de gradientes. La información geológica de superficie se tomó del Mapa Geológico de la República de Cuba 1:100000, editado por el Instituto de Geología y Paleontología en el año 2001; la información geológica del subsuelo proviene de pozos perforados en la Cuenca Central. La información geólogo–geofísica se procesó digitalmente en su totalidad. La interpretación combinada de esta información permitió un acercamiento a las características geométricas de la zona de fallas La Trocha. Se establecieron las direcciones predominantes en la zona de desplazamiento principal y la posible evolución de los esfuerzos tectónicos. Se propone un modelo de evolución para la región, considerando la existencia de una estructura en flor negativa, la cual ajusta las características existentes y explica el desarrollo simultáneo de una cuenca tensional, la Cuenca Central.

The pH-sensing receptor OGR1 improves barrier function of epithelial cells and inhibits migration in an acidic environment.

Science.gov (United States)

de Vallière, Cheryl; Vidal, Solange; Clay, Ieuan; Jurisic, Giorgia; Tcymbarevich, Irina; Lang, Silvia; Ludwig, Marie-Gabrielle; Okoniewski, Michal; Eloranta, Jyrki J; Kullak-Ublick, Gerd A; Wagner, Carsten A; Rogler, Gerhard; Seuwen, Klaus

2015-09-15

The pH-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1; GPR68) is expressed in the gut. Inflammatory bowel disease is typically associated with a decrease in local pH, which may lead to altered epithelial barrier function and subsequent gastrointestinal repair involving epithelial cell adhesion and migration. As the mechanisms underlying the response to pH changes are not well understood, we have investigated OGR1-mediated, pH-dependent signaling pathways in intestinal epithelial cells. Caco-2 cells stably overexpressing OGR1 were created and validated as tools to study OGR1 signaling. Barrier function, migration, and proliferation were measured using electric cell-substrate impedance-sensing technology. Localization of the tight junction proteins zonula occludens protein 1 and occludin and the rearrangement of cytoskeletal actin were examined by confocal microscopy. Paracellular permeability and protein and gene expression analysis using DNA microarrays were performed on filter-grown Caco-2 monolayers. We report that an acidic pH shift from pH 7.8 to 6.6 improved barrier function and stimulated reorganization of filamentous actin with prominent basal stress fiber formation. Cell migration and proliferation during in vitro wound healing were inhibited. Gene expression analysis revealed significant upregulation of genes related to cytoskeleton remodeling, cell adhesion, and growth factor signaling. We conclude that acidic extracellular pH can have a signaling function and impact the physiology of intestinal epithelial cells. The deconstruction of OGR1-dependent signaling may aid our understanding of mucosal inflammation mechanisms. Copyright © 2015 the American Physiological Society.

Los arquitectos conservadores de zona = The conservative architects of zone

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Jose Luis Javier Pérez Martín

2017-12-01

Full Text Available El conocimiento de la historia de la conservación de nuestro Patrimonio Construido, precisa del estudio del marco político y social de cada periodo, la integración de las corrientes internacionales, su adaptación, desarrollo normativo, estructuras organizativas, etc., para finalmente prestar atención a las personas que llevaron a cabo las intervenciones, entendiendo su propio debate intelectual y crítico. Entre las distintas respuestas estructuradas, encontramos un grupo de Arquitectos dotados de entidad propia, respaldados por un amplio marco legislativo, al que no se ha prestado una atención específica como grupo, aunque si a sus componentes, dada su notoriedad individual. Nos referimos a los denominados Arquitectos de Zona o Arquitectos Conservadores de Zona, cuya figura es fijada por la Ley de 1933, o mejor dicho por su Reglamento de 1936, aunque su existencia es anterior, permaneciendo hasta los albores de la Democracia. Abstract The knowledge of the history of the conservation of our Built Heritage, requires the study of the political and social framework of each period, the integration of international currents, their adaptation, normative development, organizational structures, etc., to finally pay attention to the people who carried out the interventions understanding their own intellectual and critical debate. Among the different structured responses, we find a group of architects endowed with their own entity, backed by a broad legislative framework, which has not been given specific attention as a group, although its components, given its individual notoriety. We refer to the so-called Zone Architects or Area Conservation Architects, whose figure is set by the Law of 1933, or rather by its Regulations of 1936, although its existence is earlier, remaining until the dawn of Democracy.

DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis.

Science.gov (United States)

Choi, Hyeong Sim; Lee, Kangwook; Kim, Min Kyoung; Lee, Kang Min; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

2016-04-19

Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.

Sistema de indicadores para una gestión sostenible del turismo en las zonas marino-costeras de Guatemala

OpenAIRE

Ruiz Ordóñez, Jorge Alberto

2013-01-01

Programa de doctorado: Turismo integral, interculturalidad y desarrollo sostenible [ES] El presente trabajo de investigación propone un sistema de indicadores para una gestión sostenible del turismo en las zonas marino-costeras de Guatemala.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms.

Science.gov (United States)

Lee, JeHoon; Banu, Sakhila K; Burghardt, Robert C; Starzinski-Powitz, Anna; Arosh, Joe A

2013-03-01

Endometriosis is a chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. Interactions between the endometriotic cells and the peritoneal extracellular matrix proteins (ECM) are crucial mechanisms that allow adhesion of the endometriotic cells into peritoneal mesothelia. Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. In previous studies, we have reported that selective inhibition of PGE2 receptors PTGER2 and PTGER4 decreases survival and invasion of human endometriotic epithelial and stromal cells through multiple mechanisms. Results of the present study indicates that selective inhibition of PTGER2- and PTGER4-mediated PGE2 signaling 1) decreases the expression and/or activity of specific integrin receptor subunits Itgb1 (beta1) and Itgb3 (beta3) but not Itgb5 (beta5), Itga1 (alpha1), Itga2 (alpha2), Itga5 (alpha5), and Itgav (alphav); 2) decreases integrin-signaling components focal adhesion kinase or protein kinase 2 (PTK2) and talin proteins; 3) inhibits interactions between Itgb1/Itgb3 subunits, PTK2, and talin and PTGER2/PTGER4 proteins through beta-arrestin-1 and Src kinase protein complex in human endometriotic epithelial cells 12Z and stromal cells 22B; and 4) decreases adhesion of 12Z and 22B cells to ECM collagen I, collagen IV, fibronectin, and vitronectin in a substrate-specific manner. These novel findings provide an important molecular framework for further evaluation of selective inhibition of PTGER2 and PTGER4 as potential nonsteroidal therapy to expand the spectrum of currently available treatment options for endometriosis in child-bearing age women.

Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo

Energy Technology Data Exchange (ETDEWEB)

Chian, Song; Thapa, Ruby; Chi, Zhexu [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Xiu Jun [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Tang, Xiuwen, E-mail: xiuwentang@zju.edu.cn [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China)

2014-05-16

Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed that luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC.

Desarrollo económico y migración interna en las zonas metropolitanas de México 1990-2010

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José Antonio SOBERÓN-MORA

2015-01-01

Full Text Available Este trabajo evalúa si el crecimiento económico se relaciona con el incremento de la migración de personas, como lo establece la teoría neoclásica de fines de los años sesenta y posterior. Para lograrlo, se toma un periodo que abarca veinte años, de 1990 a 2010. Se divide al país en cuatro regiones y cada una de ellas en tres sectores, en donde se consideran las 59 zonas metropolitanas definidas en el año 2012. Los resultados indican que sí existe asociación entre estas dos variables y que la relación se presenta con mayor intensidad en aquellas zonas donde se detecta un mayor crecimiento en el sector servicios, perteneciente al sureste del país.

Selección y Espaciamiento de Apartarrayos en Líneas de Distribución de 23 kV de la Zona Centro

OpenAIRE

L. Cisneros-Villalobos; F. Aquino-Roblero; M. Tecpoyotl-Torres; J. Chillopa-Linares; D. Martínez-Martínez

2015-01-01

En este artículo se analiza una red de distribución urbana de 23 kV típica de la zona central de México. El objetivo es determinar la distancia máxima de separación entre apartarrayos de línea que permita reducir las salidas de los circuitos de distribución por descargas atmosféricas directas e indirectas. Con base en las características eléctricas, ambientales, ceráunicas y geográficas de la zona, niveles de cortocircuito y las sobretensiones provocadas por maniobras rutinarias, se seleccion...

Cálculo de la evapotranspiración real diaria en la zona norte de Finlandia empleando técnicas de teledetección

OpenAIRE

Sánchez Tomás, Juan Manuel; Caselles Miralles, Vicente; Niclòs Corts, Raquel; Valor i Micó, Enric; Coll Company, César

2005-01-01

J. M. Sánchez Tomás () Hasta hace poco tiempo el estudio de la evapotranspiración (LE), fundamental en la ecuación de balance de energía, excluía zonas forestales debido a las dificultades experimentales de la toma de medidas en estas regiones. La teledetección acabó con dichas dificultades, facilitando el estudio de la LE real dentro de estas zonas, que suponen en torno a un 30% de toda la superficie terrestre. En este trabajo se presenta un método operativo para deter...

Glycosidases in porcine follicular fluid and their effect on zona pellucida-AWN 1 spermadhesin interaction.

Czech Academy of Sciences Publication Activity Database

Dráb, T.; Ren, Štěpán; Maňásková-Postlerová, Pavla; Tichá, M.; Jonáková, Věra; Liberda, J.

2017-01-01

Roč. 100, Sep 15 2017 (2017), s. 80-87 ISSN 0093-691X R&D Projects: GA ČR GA14-05547S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : glycosidases * follicle * oocyte development * zona pellucida * AWN 1 spermadhesin Subject RIV: CE - Biochemistry OBOR OECD: Biochemical research methods Impact factor: 1.986, year: 2016

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Sig; Ro, Seung-Hyun; Kim, Myungjin; Park, Hwan-Woo; Semple, Ian A.; Park, Haeli; Cho, Uhn-Soo; Wang, Wei; Guan, Kun-Liang; Karin, Michael; Lee, Jun Hee (Michigan); (UCSD)

2015-03-30

Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.

Synergistic effect of halide ions on the corrosion inhibition of aluminium in H2SO4 using 2-acetylphenothiazine

International Nuclear Information System (INIS)

Ebenso, E.E.

2003-01-01

The corrosion inhibition of aluminium in H 2 SO 4 in the presence of 2-acetylphenothiazine (2APTZ) at temperature range of 30-60 deg. C was studied using the weight loss and thermometric techniques. The effect of addition of halides (KCl, KBr, KI) is also reported. The inhibition efficiency (I, %) increased with increase in concentration of 2APTZ. The addition of the halides increased the inhibition efficiency to a considerable extent. The temperature increased the corrosion rate and inhibition efficiency in the range 30-60 deg. C in the absence and presence of the inhibitor and halides. Phenomenon of chemical adsorption is proposed. Flory-Huggins adsorption isotherm equation was obeyed at all the concentrations studied. The decrease in inhibition efficiency (and surface coverage values) was found to be in the order I - >Br - >Cl - which clearly indicates that the radii and the electronegativity of halides play a significant role in the adsorption process. All the data acquired reveal that 2APTZ acts as an inhibitor in the acid environment from the two techniques used. The synergistic effect of 2APTZ and halide ions is discussed

Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes.

Science.gov (United States)

Bae, Soo Hyeon; Kwon, Min Jo; Choi, Eu Jin; Zheng, Yu Fen; Yoon, Kee Dong; Liu, Kwang-Hyeon; Bae, Soo Kyung

2013-09-05

The present study was performed to evaluate the potency and specificity of sibutramine as an inhibitor of the activities of nine human CYP isoforms in liver microsomes. Using a cocktail assay, the effects of sibutramine on specific marker reactions of the nine CYP isoforms were measured in human liver microsomes. Sibutramine showed potent inhibition of CYP2B6-mediated bupropion 6-hydroxylation with an IC50 value of 1.61μM and Ki value of 0.466μM in a competitive manner at microsomal protein concentrations of 0.25mg/ml; this was 3.49-fold more potent than the typical CYP2B6 inhibitor thio-TEPA (Ki=1.59μM). In addition, sibutramine slightly inhibited CYP2C19 activity (Ki=16.6μM, noncompetitive inhibition) and CYP2D6 activity (Ki=15.7μM, noncompetitive inhibition). These observations indicated 35.6- and 33.7-fold decreases in inhibition potency, respectively, compared with that of CYP2B6 by sibutramine. However, no inhibition of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, or CYP2E1 activities was observed. In addition, the CYP2B6 inhibitory potential of sibutramine was enhanced at a lower microsomal protein concentration of 0.05mg/ml. After 30min preincubation of human liver microsomes with sibutramine in the presence of NADPH, no shift in IC50 was observed in terms of inhibition of the activities of the nine CYPs, suggesting that sibutramine is not a time-dependent inactivator. These observations suggest that sibutramine is a selective and potent inhibitor of CYP2B6 in vitro, whereas inhibition of other CYPs is substantially lower. These in vitro data support the use of sibutramine as a well-known inhibitor of CYP2B6 for routine screening of P450 reversible inhibition when human liver microsomes are used as the enzyme source. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

Science.gov (United States)

Holland, M L; Lau, D T T; Allen, J D; Arnold, J C

2007-11-01

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro. Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2. Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays. The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting. CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line. The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent. The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition. Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression. Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation.

Science.gov (United States)

Kirschning, Carsten J; Dreher, Stefan; Maass, Björn; Fichte, Sylvia; Schade, Jutta; Köster, Mario; Noack, Andreas; Lindenmaier, Werner; Wagner, Hermann; Böldicke, Thomas

2010-04-13

Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (alphaT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. alphaT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser)3 amino acid sequence. Coexpression of alphaT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with alphaT2ib indicated interaction of alphaT2ib with its cognate antigen within cells. alphaT2ib inhibited NF-kappaB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding alphaT2ib into HEK293 cells demonstrated high efficiency of the TLR2-alphaT2ib interaction. The alphaT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV)-alphaT2ib. Transduction with AdValphaT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM). Furthermore, TLR2 activation dependent TNFalpha mRNA accumulation, as

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

African Journals Online (AJOL)

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

Inventario de emisiones de contaminantes atmosféricos convencionales en la zona de Cali-Yumbo

Directory of Open Access Journals (Sweden)

Mauricio Jaramillo

2004-01-01

Full Text Available En este artículo se presenta el resultado de la cuantificación y cualificación de contaminantes atmosféricos convencionales (COV, MP10, CO, NOx y SOx emitidos por fuentes antropogénicas para el año 1997 en la zona urbana de Cali-Yumbo (Colombia. Se consideraron fuentes de área, puntuales y móviles. Para las fuentes puntuales se utilizó información en las declaraciones entregadas a las autoridades ambientales por 108 empresas del área. Se utilizó además el método de factores de emisión para relacionar el nivel de actividad productiva con la emisión de contaminantes, y se aplicó el modelo MOBILE 6.0 para calcular las emisiones de fuentes móviles. El trabajo será de utilidad para generar proyectos en áreas de gestión ambiental urbana, desarrollar modelos para la dispersión de contaminantes y aportar criterios para mejor monitoreo y predicción de la calidad del aire en la zona de interés.

Urbanismo, Arquitectura y Legislación: la ley de Zonas Polémicas y su incidencia en Ultramar (Melilla, 1910

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Salvador Gallego Aranda

2009-12-01

Full Text Available La urbanización de la calle del General Chacel (Barrio de la Reina Victoria, Melilla, pone de manifiesto las dificultades derivadas, en cualquier tipo de expansión poblacional y su planeamiento urbano, de la entonces vigente Ley de Zonas Polémicas. La extensión de trescientos metros concedidos como zona de defensa, consecuencia de dicha disposición, motiva que su arteria vital, correspondiente al centro de la ciudad por excelencia, sea lo último en urbanizarse. El análisis de la construcción de sus solares, deja de manifiesto el entramado de preceptos legales, condiciones constructivas, artífices diversos y promotores nacionales señeros implicados en el crecimiento de Melilla.

CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells.

Science.gov (United States)

Ito, Saya; Ueno, Akihisa; Ueda, Takashi; Nakagawa, Hideo; Taniguchi, Hidefumi; Kayukawa, Naruhiro; Fujihara-Iwata, Atsuko; Hongo, Fumiya; Okihara, Koji; Ukimura, Osamu

2018-04-03

The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination.

Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.

Science.gov (United States)

Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M; Gish, Gerald D; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio

2011-10-14

Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention. Copyright © 2011 Elsevier Inc. All rights reserved.

Glycosidases in porcine follicular fluid and their effect on zona pellucida-AWN 1 spermadhesin interaction

Czech Academy of Sciences Publication Activity Database

Dráb, T.; Ren, Štěpán; Maňásková-Postlerová, Pavla; Tichá, M.; Jonáková, Věra; Liberda, J.

2017-01-01

Roč. 100, SEP 15 2017 (2017), s. 80-87 ISSN 0093-691X R&D Projects: GA ČR GA14-05547S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Glycosidases * Oocyte development * Zona pellucida * Follicle Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 1.986, year: 2016

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

Science.gov (United States)

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Inhibition of fatty acid synthesis in isolated adipocytes by 5-(tetradecyloxy)-2-furoic acid.

Science.gov (United States)

Halvorson, D L; McCune, S A

1984-11-01

The compound 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, inhibits fatty acid synthesis, lactate and pyruvate accumulation and CO2 release in isolated rat adipocytes. TOFA stimulates the accumulation of citrate. ATP levels are not lowered by TOFA. In comparison with the natural fatty acid, oleate, TOFA exhibited a much greater inhibitory effect on lipogenesis. TOFyl-CoA formation within intact adipocytes was demonstrated. Although not inhibited by TOFA, acetyl-CoA carboxylase is inhibited by TOFyl-CoA. It is proposed that many of the metabolic effects of TOFA in isolated adipocytes can be explained by TOFyl-CoA inhibition of acetyl-CoA carboxylase. TOFA inhibits glycolysis as a secondary event with the primary event of inhibition of fatty acid synthesis causing an accumulation of citrate which is an inhibitor of phosphofructokinase.

MDM2 binds and inhibits vitamin D receptor

OpenAIRE

Heyne, Kristina; Heil, Tessa-Carina; Bette, Birgit; Reichrath, Jörg; Roemer, Klaus

2015-01-01

The E3 ubiquitin ligase and transcriptional repressor MDM2 is a potent inhibitor of the p53 family of transcription factors and tumor suppressors. Herein, we report that vitamin D receptor (VDR), another transcriptional regulator and probably, tumor suppressor, is also bound and inhibited by MDM2. This interaction was not affected by vitamin D ligand. VDR was ubiquitylated in the cell and its steady-state level was controlled by the proteasome. Strikingly, overproduced MDM2 reduced the level ...

Oocytes with a dark zona pellucida demonstrate lower fertilization, implantation and clinical pregnancy rates in IVF/ICSI cycles.

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Wei Shi

Full Text Available The morphological assessment of oocytes is important for embryologists to identify and select MII oocytes in IVF/ICSI cycles. Dysmorphism of oocytes decreases viability and the developmental potential of oocytes as well as the clinical pregnancy rate. Several reports have suggested that oocytes with a dark zona pellucida (DZP correlate with the outcome of IVF treatment. However, the effect of DZP on oocyte quality, fertilization, implantation, and pregnancy outcome were not investigated in detail. In this study, a retrospective analysis was performed in 268 infertile patients with fallopian tube obstruction and/or male factor infertility. In 204 of these patients, all oocytes were surrounded by a normal zona pellucida (NZP, control group, whereas 46 patients were found to have part of their retrieved oocytes enclosed by NZP and the other by DZP (Group A. In addition, all oocytes enclosed by DZP were retrieved from 18 patients (Group B. No differences were detected between the control and group A. Compared to the control group, the rates of fertilization, good quality embryos, implantation and clinical pregnancy were significantly decreased in group B. Furthermore, mitochondria in oocytes with a DZP in both of the two study groups (A and B were severely damaged with several ultrastructural alterations, which were associated with an increased density of the zona pellucida and vacuolization. Briefly, oocytes with a DZP affected the clinical outcome in IVF/ICSI cycles and appeared to contain more ultrastructural alterations. Thus, DZP could be used as a potential selective marker for embryologists during daily laboratory work.

Geomorfología, zonas de erosión y sedimentación costera de la Península de Burica, Costa Rica

OpenAIRE

Rojas Herrera, Vanessa

2015-01-01

Resumen Se efectuó una evaluación geomorfológica y de zonas de erosión y sedimentación del sector oeste de la Península, desde punta Banco hasta punta El Mangle, con el fin de determinar aspectos relevantes desde el punto de vista geológico. El estudio se llevo a cabo durante 9 días en enero del 2008, tiempo en el cual, se realizó el estudio geológico, geomorfológico y de zonas de erosión-sedimentación costera, presentándose en este trabajo solamente los resultados relevantes de los últimos d...

Metodología de análisis multiobjetivo supervisado para la priorización de zonas de intervención y proyectos en cuenca hidrográficas.

OpenAIRE

Jaramillo Álvarez, Gloria Patricia; Smith Quintero, Ricardo Agustín; Vélez Upegui, Jaime Ignacio

2004-01-01

Se presenta una propuesta metodológica para la priorización de zonas de intervención y proyectos a realizar en esas zonas, en un programa de ordenamiento de cuencas, con base en un método de análisis multicriterio bajo incertidumbre. La metodología se aplica a la cuenca urbana La Iguana [Antioquia, Colombia], la cual presenta graves problemas ambientales y sociales.

Proyectos de desarrollo rural en zonas marginadas de Mexico usando ingenieria concurrente

OpenAIRE

González Almaguer, Carlos Alberto; Montejano, Gerardo; Vázquez Feijoo, Horacio; Nieto Barrera, Jorge; Lloveras Macià, Joaquín

2012-01-01

La Ingeniería concurrente (CE) ha atraído más atención en los últimos años debido a que su aplicación reduce el tiempo de diseño de productos desde su concepción hasta su manufactura masiva, mejorando la calidad y el desempeño de los equipos de trabajo en la organización rompiendo las barreras de la ingeniería secuencial. El presente documento muestra una metodología para la realización de proyectos rurales con nuevos productos agroindustriales o su innovación en zonas marginad...

Formas de hierro y aluminio en suelos con diferentes usos en la zona norte del departamento del Magdalena, Colombia

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José Rafael Vásquez Polo

2014-12-01

Full Text Available En el estudio se evaluaron las diferentes formas de hierro (Fe y aluminio (Al presentes en suelos cultivados y en áreas de bosque de la zona norte del departamento del Magdalena (Colombia. Se seleccionaron seis zonas de muestreo localizadas entre 0 y 1000 m.s.n.m. Se utilizaron tres técnicas selectivas de extracción de Fe y Al con los agentes extractantes: pirofosfato de sodio, oxalato ácido de amonio, y ditionito citrato bicarbonato. Los contenidos totales de Fe y Al fueron determinados mediante un ataque ácido y cuantificación por absorción atómica. El análisis de varianza multivariado mostró diferencias significativas (P 3% del Al total, lo que sugiere que un alto contenido de Al forma parte de estructuras cristalinas.

Zonas mortas na cóclea em freqüências altas: implicações no processo de adaptação de prótese auditivas Dead regions in the cochlea at high frequencies: implications for the adaptation to hearing aids

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Angela Gordo

2007-06-01

Full Text Available Em perdas auditivas de grau moderado a severo nas freqüências altas, a lesão coclear pode estar relacionada a "zonas mortas", regiões onde as células ciliadas internas e/ou neurônios adjacentes não são funcionais. OBJETIVO: Avaliar o reconhecimento de fala em pacientes com e sem zonas mortas na cóclea em freqüências altas. MATERIAL e MÉTODO: Estudo clínico e experimental de 30 indivíduos adultos, distribuídos em dois grupos: grupo 1 - 15 indivíduos sem zonas mortas, e grupo 2 - 15 com zonas mortas na cóclea. Os pacientes foram submetidos à pesquisa do índice de reconhecimento de fala, limiar de reconhecimento de sentenças, sem e com ruído competitivo. Os testes de fala foram realizados sem prótese, com próteses auditivas amplificando a faixa de freqüências de 100 a 8000 Hz (programa 1 e com amplificação restrita, 100 a 2560 Hz (programa 2. RESULTADOS: O grupo 1 apresentou melhor desempenho utilizando as próteses auditivas no programa 1. Já o grupo 2 obteve melhor desempenho com o programa 2. CONCLUSÕES: Pacientes sem zonas mortas na cóclea obtêm maior benefício com a amplificação em freqüências altas. Na presença de zonas mortas em freqüências altas, o melhor desempenho é obtido com a amplificação restrita nestas freqüências.In patients with moderate to severe high-frequency hearing loss, cochlear damage may include "dead regions" where there are no functional inner hair cells and/or associated neurons. AIM: This study examines speech recognition in sensorineural impaired hearing patients with and without cochlear dead regions at high frequencies. METHODS: a clinical and experimental study was made of thirty patients with sensorineural hearing loss that were classified into two groups: group 1 - included 15 subjects with hearing loss and no dead regions; and group 2 - included 15 subjects with dead regions in the cochlea at high frequencies. Patients undertook word recognition score and speech

Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation

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Lindenmaier Werner

2010-04-01

Full Text Available Abstract Background Toll-like receptor (TLR 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib which was generated from an antagonistic monoclonal antibody (mAb towards human and murine TLR2 (T2.5 to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser3 amino acid sequence. Results Coexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM. Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well

GRAMÍNEAS TROPICALES EN EL ENGORDE DE CUYES MEJORADOS SEXADOS (Cavia porcellus Linnaeus EN LA ZONA DE LA MANÁ

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Adolfo Sánchez Laiño

2009-06-01

Full Text Available La investigación de gramíneas tropicales en el engorde de cuyes en la zona de La Maná. La misma que persiguió los siguientes objetivos: Incrementar los índices productivos en cuyes (Cavia porcellus Linnaeus peruanos mejorados bajo el efecto del consumo del pasto saboya (Panicum maximun Jack, hojas de maíz (Zea mays y caña de azúcar (Saccharum officinarum L en la zona de La Maná, y determinar la rentabilidad de los tratamientos. Se utilizaron 48 cuyes peruanos mejorados sexados de 35 días de edad con un peso promedio de 305 g. Se aplicó un arreglo factorial 2 (sexo x 3 (gramíneas con cuatro repeticiones, dentro de un (DBCA. Para las comparaciones entre medidas se utilizó la prueba de Tukey al 0.05% de probabilidad. Para obtener la rentabilidad de los tratamientos se utilizó la Relación Beneficio–Costo. Se evaluó el: consumo de gramíneas (g, consumo de alimento (g, ganancia de peso (g, conversión alimenticia, peso vivo (g y rendimiento a la canal (%. Los cuyes machos presentaron el mayor (P0.05 no se vio afectado por el efecto del consumo de gramíneas. La mayor rentabilidad la registraron los cuyes machos alimentados con hoja de maíz + balanceado (52.4%.

Cyclooxgenase-2 inhibiting perfluoropoly (ethylene glycol ether theranostic nanoemulsions-in vitro study.

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Sravan Kumar Patel

Full Text Available Cylcooxgenase-2 (COX-2 expressing macrophages, constituting a major portion of tumor mass, are involved in several pro-tumorigenic mechanisms. In addition, macrophages are actively recruited by the tumor and represent a viable target for anticancer therapy. COX-2 specific inhibitor, celecoxib, apart from its anticancer properties was shown to switch macrophage phenotype from tumor promoting to tumor suppressing. Celecoxib has low aqueous solubility, which may limit its tumor inhibiting effect. As opposed to oral administration, we propose that maximum anticancer effect may be achieved by nanoemulsion mediated intravenous delivery. Here we report multifunctional celecoxib nanoemulsions that can be imaged by both near-infrared fluorescence (NIRF and (19F magnetic resonance. Celecoxib loaded nanoemulsions showed a dose dependent uptake in mouse macrophages as measured by (19F NMR and NIRF signal intensities of labeled cells. Dramatic inhibition of intracellular COX-2 enzyme was observed in activated macrophages upon nanoemulsion uptake. COX-2 enzyme inhibition was statistically equivalent between free drug and drug loaded nanoemulsion. However, nanoemulsion mediated drug delivery may be advantageous, helping to avoid systemic exposure to celecoxib and related side effects. Dual molecular imaging signatures of the presented nanoemulsions allow for future in vivo monitoring of the labeled macrophages and may help in examining the role of macrophage COX-2 inhibition in inflammation-cancer interactions. These features strongly support the future use of the presented nanoemulsions as anti-COX-2 theranostic nanomedicine with possible anticancer applications.

Caspase-dependent inhibition of store-operated Ca2+ entry into apoptosis-committed Jurkat cells

International Nuclear Information System (INIS)

Onopiuk, Marta; Wierzbicka, Katarzyna; Brutkowski, Wojciech; Szczepanowska, Joanna; Zablocki, Krzysztof

2010-01-01

Activation of T-cells triggers store-operated Ca 2+ entry, which begins a signaling cascade leading to induction of appropriate gene expression and eventually lymphocyte proliferation and differentiation. The simultaneous enhancement of Fas ligand gene expression in activated cells allows the immune response to be limited by committing the activated cells to apoptosis. In apoptotic cells the store-operated calcium entry is significantly inhibited. It has been documented that moderate activation of Fas receptor may cause reversible inhibition of store-operated channels by ceramide released from hydrolyzed sphingomyelin. Here we show that activation of Fas receptor in T-cells results in caspase-dependent decrease of cellular STIM1 and Orai1 protein content. This effect may be responsible for the substantial inhibition of Ca 2+ entry into Jurkat cells undergoing apoptosis. In turn, this inhibition might prevent overloading of cells with calcium and protect them against necrosis. -- Research highlights: → Fas activation reduces STIM1 and Orai1 protein content in caspase dependent manner. → Fas activation partially reduces mitochondrial potential in caspase dependent manner. → Fas stimulation inhibits of store-operated Ca 2+ entry in caspase dependent manner. → Inhibition of Ca 2+ entry in apoptotic cells may protect them from secondary necrosis.

La zona de reserva campesina del valle del río Cimitarra: un ejercicio inconcluso de participación ciudadana y manejo colectivo del territorio

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Andrés Leonardo Molina Portuguez

2011-07-01

Full Text Available Cuadernos de Geografía: Revista Colombiana de Geografía Cuad. Geogr. Rev. Colomb. Geogr., Volumen 20, Número 2, p. 21 - 33, 2011. ISSN electrónico 2256-5442. ISSN impreso 0121-215X. La zona de reserva campesina del valle del río Cimitarra: un ejercicio inconcluso de participación ciudadana y manejo colectivo del territorio A zona de reserva camponesa do vale do rio Cimitarra: um exercício inconcluso de participação cidadã e manejo colectivo do território The Cimitarra River Valley Rural Reserve Zone: An Unfinished Exercise in Citizen Participation and Collective Management of Territory Andrés Leonardo Molina Portuguez* Universidad Nacional de Colombia, Bogotá *Ingeniero Forestal, actualmente cursa estudios de Maestría en Geografía en la Universidad Nacional de Colombia. Su proyecto de tesis estudia el fenómeno de los cultivos de uso ilícito en Colombia. Ha sido ponente en congresos nacionales relacionados con biodiversidad y el ordenamiento del territorio. Se ha desempeñado profesionalmente en investigaciones sobre bosques tropicales, programas de desarrollo alternativo, proyectos de ordenamiento territorial y ambiental. Dirección postal: carrera 72J Bis n.° 40C-50. Interior 2, apt. 302. Alamedas de Timiza I. Bogotá. Colombia. Correo electrónico: lmportuguez@gmail.com; almolinap@unal.edu.co Recibido: 14 de marzo del 2011. Aceptado: 30 de mayo del 2011 Artículo de investigación sobre los problemas para la planeación y gestión territorial participativa en la zona de reserva del río Cimitarra en Colombia. Resumen La zona de reserva campesina del valle del río Cimitarra (ZRC fue creada con el objetivo de estabilizar la economía campesina y crear un espacio participativo de ordenamiento territorial rural. Sin embargo, cuatro meses después de su creación la ZRC fue suspendida por el Gobierno nacional. En este contexto, el artículo analiza algunos elementos necesarios para llevar a cabo la planeación territorial como

Kinetics and mechanism of jack bean urease inhibition by Hg2+

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Du Nana

2012-12-01

Full Text Available Abstract Background Jack bean urease (EC 3.5.1.5 is a metalloenzyme, which catalyzes the hydrolysis of urea to produce ammonia and carbon dioxide. The heavy metal ions are common inhibitors to control the rate of the enzymatic urea hydrolysis, which take the Hg2+ as the representative. Hg2+ affects the enzyme activity causing loss of the biological function of the enzyme, which threatens the survival of many microorganism and plants. However, inhibitory kinetics of urease by the low concentration Hg2+ has not been explored fully. In this study, the inhibitory effect of the low concentration Hg2+ on jack bean urease was investigated in order to elucidate the mechanism of Hg2+ inhibition. Results According to the kinetic parameters for the enzyme obtained from Lineweaver–Burk plot, it is shown that the Km is equal to 4.6±0.3 mM and Vm is equal to 29.8±1.7 μmol NH3/min mg. The results show that the inhibition of jack bean urease by Hg2+ at low concentration is a reversible reaction. Equilibrium constants have been determined for Hg2+ binding with the enzyme or the enzyme-substrate complexes (Ki =0.012 μM. The results show that the Hg2+ is a noncompetitive inhibitor. In addition, the kinetics of enzyme inhibition by the low concentration Hg2+ has been studied using the kinetic method of the substrate reaction. The results suggest that the enzyme first reversibly and quickly binds Hg2+ and then undergoes a slow reversible course to inactivation. Furthermore, the rate constant of the forward reactions (k+0 is much larger than the rate constant of the reverse reactions (k-0. By combining with the fact that the enzyme activity is almost completely lost at high concentration, the enzyme is completely inactivated when the Hg2+ concentration is high enough. Conclusions These results suggest that Hg2+ has great impacts on the urease activity and the established inhibition kinetics model is suitable.

Corrosion inhibition of nickel in H2SO4 solution by alanine

International Nuclear Information System (INIS)

Hamed, E.; Abd El-REhim, S.S.; El-Shahat, M.F.; Shaltot, A.M.

2012-01-01

Highlights: ► Corrosion of Ni in 1 M H 2 SO 4 in the absence and the presence of alanine. ► Alanine acts as a moderate mixed type inhibitor. ► Physical adsorption of alanine and formation of protective film are on Ni surface. ► Addition of KI improves the inhibition efficiency (synergistic effect). ► EFM technique is in reasonably good agreement with the different techniques used. - Abstract: The effect of alanine, as a safe inhibitor, was studied by measuring the corrosion of Ni in aerated and stagnant 1 M H 2 SO 4 solution (pH ∼0.2). Measurements were performed under various conditions using potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and the new electrochemical frequency modulation (EFM) methods. The obtained results showed that the addition of alanine alone gives a moderate inhibition and acts as an anodic-type inhibitor. The inhibition is due to physical adsorption of alanine on the metal surface. The inhibition efficiency enhances with increasing alanine concentration and immersion time but decreases with rise in temperature. The apparent activation energy, E a , is higher in the presence than in the absence of alanine. Addition of I − ions greatly improves the inhibition efficiency of alanine. The synergistic effect is due to enhanced adsorption of alanine cations by chemisorbed I − anions on the metal surface. The results obtained from polarization, EIS and EFM techniques are in good agreement indicating that EFM method can be used successfully for monitoring corrosion rate of Ni in H 2 SO 4 solution with and without alanine.

MUCHO Y MUY BUEN VINO. PRODUCCIÓN VITIVINÍCOLA EN LA ZONA NORTE DE SANTIAGO (SIGLOS XVI -XVIII

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Carlos Ruiz Rodríguez

2011-10-01

Full Text Available En la zona norte de Santiago (sectores de la Chimba, Renca, Conchalí, El Salto, Quilicura, se comenzó a producir desde poco después de la conquista española, “mucho y muy buen vino”. Se reseña el origen y particularidades de esta producción vinícola durante el período colonial. Se reconstruye un cuadro descriptivo de la viñatería colonial en la zona, junto con analizar los aspectos económicos: la evolución de la infraestructura productiva, el tipo de predios dedicados a la producción de vino, el precio de los suelos y de las plantas de viña, el uso de mano de obra (asalariada, servil y esclava y el impacto del establecimiento del régimen colonial y del consumo de alcohol en la población indígena.

ANÁLISE MULTICRITERIAL APLICADA A ELABORAÇÃO DE ZONEAMENTO DE UNIDADE DE CONSERVAÇÃO NA ZONA COSTEIRA DA BAHIA, BRASIL

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Elfany Reis do Nascimento Lopes

2016-08-01

Full Text Available Este estudo objetivou demonstrar a aplicação da análise multicriterial (AMC na elaboração do zoneamento de unidades de conservação situadas na zona costeira do Brasil, utilizando a Área de Proteção Ambiental de Guaibim como exemplo na elaboração de um zoneamento que compatibilizasse conservação dos recursos naturais e desenvolvimento local. A análise multicriterial foi utilizada para adequar a APA à conservação e ao desenvolvimento, através do estabelecimento de critérios advindos do mapa de uso da terra e da ponderação dos pesos de importância pela técnica processo de análise hierárquica e da agregação dos fatores pela técnica da combinação linear ponderada. O mapa de viabilidade à conservação apresentou maiores escores de viabilidade nos extremos territoriais, com áreas de manguezais, brejos, restingas e rios. O mapa de viabilidade ao desenvolvimento sugeriu maiores escores para o centro da APA. Posteriormente, os mapas gerados foram integrados através da análise multiobjetivo, eliminando os conflitos e acomodando as áreas adequadas a cada objetivo. A Análise multiobjetivo sugeriu cerca de 70% da área para a conservação e a área de desenvolvimento foi delimitada a 30% do território, culminando em duas principais zonas de manejo (Zona de Conservação e Zona de Desenvolvimento e as respectivas subzonas de manejo. A AMC é uma análise robusta e flexível e é indicada na elaboração de zoneamentos de unidades de conservação ou ainda, na atualização destes.

The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

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Dhananjaya, Bhadrapura Lakkappa; Sudarshan, Shivalingaiah; Dongol, Yashad; More, Sunil S

2016-05-01

The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent.

Swallowing Quality of Life After Zona Incerta Deep Brain Stimulation.

Science.gov (United States)

Sundstedt, Stina; Nordh, Erik; Linder, Jan; Hedström, Johanna; Finizia, Caterina; Olofsson, Katarina

2017-02-01

The management of Parkinson's disease (PD) has been improved, but management of signs like swallowing problems is still challenging. Deep brain stimulation (DBS) alleviates the cardinal motor symptoms and improves quality of life, but its effect on swallowing is not fully explored. The purpose of this study was to examine self-reported swallowing-specific quality of life before and after caudal zona incerta DBS (cZI DBS) in comparison with a control group. Nine PD patients (2 women and 7 men) completed the self-report Swallowing Quality of Life questionnaire (SWAL-QOL) before and 12 months after cZI DBS surgery. The postoperative data were compared to 9 controls. Median ages were 53 years (range, 40-70 years) for patients and 54 years (range, 42-72 years) for controls. No significant differences were found between the pre- or postoperative scores. The SWAL-QOL total scores did not differ significantly between PD patients and controls. The PD patients reported significantly lower scores in the burden subscale and the symptom scale. Patients with PD selected for cZI DBS showed good self-reported swallowing-specific quality of life, in many aspects equal to controls. The cZI DBS did not negatively affect swallowing-specific quality of life in this study.

inhibitive action and synergistic performance of 2-amino

African Journals Online (AJOL)

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The corrosion inhibition action of copper alloy in 1 M HCl solution in the presence of 2- ... application of copper alloy is enormous due to their properties such as good corrosion resistance, mechanical work ability and better thermal conductivity. ... CR = (1) where K the constant is given as 87.6. Element. Al. Sn. Mn. Mg. S. P.

Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation.

Science.gov (United States)

Avanzi, Mauro P; Goldberg, Francine; Davila, Jennifer; Langhi, Dante; Chiattone, Carlos; Mitchell, William Beau

2014-03-01

The processes of megakaryocyte polyploidization and demarcation membrane system (DMS) formation are crucial for platelet production, but the mechanisms controlling these processes are not fully determined. Inhibition of Rho kinase (ROCK) signalling leads to increased polyploidization in umbilical cord blood-derived megakaryocytes. To extend these findings we determined the effect of ROCK inhibition on development of the DMS and on proplatelet formation. The underlying mechanisms were explored by analysing the effect of ROCK inhibition on the expression of MYC and NFE2, which encode two transcription factors critical for megakaryocyte development. ROCK inhibition promoted DMS formation, and increased proplatelet formation and platelet release. Rho kinase inhibition also downregulated MYC and NFE2 expression in mature megakaryocytes, and this down-regulation correlated with increased proplatelet formation. Our findings suggest a model whereby ROCK inhibition drives polyploidization, DMS growth and proplatelet formation late in megakaryocyte maturation through downregulation of MYC and NFE2 expression. © 2014 John Wiley & Sons Ltd.

Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase

DEFF Research Database (Denmark)

Thastrup, Ole; Cullen, P J; Drøbak, B K

1990-01-01

. This hypothesis is strongly supported by the demonstration that thapsigargin causes a rapid inhibition of the Ca2(+)-activated ATPase activity of rat liver microsomes, with an identical dose dependence to that seen in whole cell or isolated microsome Ca2+ discharge. The inhibition of the endoplasmic reticulum...

Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth.

Science.gov (United States)

Chen, Jun; Kinoshita, Taisei; Sukbuntherng, Juthamas; Chang, Betty Y; Elias, Laurence

2016-12-01

Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK. Irreversible inhibition of HER2 and EGFR in breast cancer cells was established after 30-minute incubation above 100 nmol/L or following 2-hour incubation at lower concentrations. Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction. The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK. Xenograft studies with HER2 + MDA-MB-453 and BT-474 cells in mice in conjunction with determination of pharmacokinetics demonstrated significant exposure-dependent inhibition of growth and key signaling molecules at levels that are clinically achievable. Ibrutinib's unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology. Mol Cancer Ther; 15(12); 2835-44. ©2016 AACR. ©2016 American Association for Cancer Research.

Modelo de indicadores para la evaluación y monitoreo del desarrollo sustentable en la zona costera de Mahahual, Quintana Roo, México

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Lourdes Castillo Villanueva

2016-01-01

Full Text Available La evaluación y el monitoreo del desarrollo sustentable de las zonas costeras son fundamentales para conocer los retos por enfrentar, así como para determinar las estrategias que deban implementarse para su atención. Se propone un marco conceptual y un modelo de indicadores para evaluar el desarrollo de una zona costera. Se generó el índice de desarrollo sustentable para Mahahual obteniendo un valor de 0,40, que representa un nivel bajo de sustentabilidad, lo que indica que se debe poner especial atención en minimizar los factores de presión que se están presentando específicamente en dos zonas de interacción. Entre los desafíos para la sustentabilidad de Mahahual se encuentra diseñar políticas públicas adecuadas a las condiciones de la región, aplicar correctamente los instrumentos normativos y de planeación del territorio, mejorar la calidad de vida de la comunidad, reducir el impacto de las actividades turísticas y ordenar las actividades y usos en el ambiente marino.

CONTENIDO DE POLIAMINAS LIBRES EN PALMAS AFECTADAS POR PUDRICION DEL COGOLLO EN LAS ZONAS CENTRAL Y OCCIDENTAL DE COLOMBIA

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Hernán Mauricio Romero

2010-01-01

Full Text Available La pudrición del cogollo (PC es la principal enfermedad de la palma en Colombia. En las zonas palmeras Central (ZC y Oriental (ZE, las palmas enfermas pueden recuperarse naturalmente. En la Zona Occidental (ZW el proceso de recuperación no es evidente. La recuperación de palmas está ligada a gran actividad meristemática que podría involucrar la acción inductora de metabolitos como las poliaminas (PA. Este trabajo muestra la relación entre poliaminas del meristemo y la capacidad de recuperación de palmas con PC, en dos zonas agroclimáticas diferentes. Poliaminas extraídas del meristemo de palmas sembradas en ZC y ZW, fueron analizadas por HPLC. En ZC, donde existe recuperación espontánea, los niveles más altos de PA se presentan en palmas sanas y en recuperación y a medida que avanza la enfermedad la concentración desciende hasta un mínimo en el estado de PC inicial (PCI. Luego la concentración de PA aumenta hasta el estado de Buena Recuperación (BR donde los valores de poliaminas son más altos que los de palmas sanas. En la ZW, con la enfermedad el contenido de PA aumenta llegando al máximo en plantas sin recuperación y el mínimo se presenta en plantas sanas. Las diferencias entre zonas pueden explicarse por diferentes roles de las poliaminas en plantas. En la ZC la cantidad elevada de PA en palmas sanas o en recuperación funcionaría en la inducción de actividad meristemática, para la recuperación espontánea. En la ZW el aumento en el contenido de PA con la enfermedad induciría la generación de especies reactivas de oxígeno para defensa secundaria de la planta ante la imposibilidad de, a través de incrementos en la actividad meristemática producir rápidamente estructuras sanas que no sean reinfectadas.

Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma.

Science.gov (United States)

Wang, Ying; Wang, Bo; Li, Peng; Zhang, Qi; Liu, Pinan

2017-12-01

Objective To study the function and potential mechanism of RAC1 inhibitors in NF2-associated schwannoma. Methods In this study, we the downregulation of RAC1 activity and tumor cell phenotypes by RAC1 inhibitor NSC23766 in vitro. And we further validated the anti-proliferation effect by this RAC1 inhibitor in subcutaneous xenograft tumor model and sciatic nerve model. Results Pharmacological inhibition of RAC1 could significantly inhibit the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inducing apoptosis. Pharmacological inhibition of RAC1 effectively reduced Rac1 activity and down-regulated the pathway downstream of Rac. Moreover, pharmacological inhibition of RAC1 showed a potential antitumor effect, with low toxicity in vivo. Conclusion RAC1 inhibitors may play a therapeutic role in patients with schwannoma.

Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells.

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Junping Ren

Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS. Whether M2-2 regulates the innate immunity in human dendritic cells (DC, an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-ΔM2-2 produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT, suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88, an essential adaptor for Toll-like receptors (TLRs, plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface*

Science.gov (United States)

Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

2016-01-01

Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. PMID:26912659

Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface.

Science.gov (United States)

Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

2016-04-15

Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Some Anilides of 2-Alkylthio- and 2-Chloro-6-Alkylthio-4-Pyridinecarboxylic Acids: Synthesis and Photosynthesis-Inhibiting Activity

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Miloš Macháček

2001-06-01

Full Text Available Many compounds containing a -CONH- group display photosynthesis inhibiting activity. Based on this structural feature, a group of anilides of 2-alkylthio-(1b-4f or 2-chloro-6-alkylthio-4-pyridinecarboxylic acids (5a-6c was synthesised. The prepared compounds were tested for their inhibition of the oxygen evolution rate (OER in spinach chloroplasts. A quasi-parabolic dependence between photosynthesis-inhibiting activity and the lipophilicity of the compounds was determined for 1b-4f as well as for 5a-6c. The inhibitory activity of compounds 1b-4f was higher than that of 5a-6c for comparable lipophilicity values.

Sprout inhibition of potatoes by electron irradiation, (2)

International Nuclear Information System (INIS)

Furuta, Junichiro; Hiraoka, Eiichi; Okamoto, Shinichi; Fujishiro, Masatoshi; Kanazawa, Tamotsu; Ohnishi, Tokuhiro; Tsujii, Yukio; Hori, Shiro

1982-01-01

Sprouting of potatoes are inhibited usually by the gamma-ray irradiation. The buds of potatoes exist in a very thin layer near surface of each tuber. So the inhibition will be performed sufficiently by surface irradiation using electron beams. To irradiate all surfaces of each potato uniformly, the authors prepare a new apparatus which is a conveyer passing under an electron beam scanner of accelerator rotating the potatoes by many rotating rollers. The sprout inhibition experiment of potatoes was performed by following three methods to obtain the performance of this apparatus, and the results were compared. 1) turn over irradiation method --- potatoes were arranged in one layer in plastic baskets and were irradiated on the conveyor. After irradiation, the potatoes were turned over and were irradiated again. 2) rotating irradiation method --- potatoes were rotated on the rotating roller apparatus set on the conveyer and were passed under the electron beam scanner. 3) rotating irradiation method with an improved rotating roller apparatus --- the rotating rollers have many protuberances on their surface to irradiate all of potato surface more uniform. 550 keV electron beams by Cockcroft-Walton type accelerator were used for the irradiation and the irradiated dose was 5 to 20 krad. 40 pieces of potates, ''Danshaku'' variety yielded in June 1981, were irradiated for each dose in the beginning of August. Prior to these irradiation experiments, the dose and dose uniformity were checked by the agar color dosimeters. After the irradiation, potatoes were stored in natural condition and their sprouting was observed. The potatoes irradiated by the improved rotating roller apparatus were almost completely sprout-inhibited by 20 krad irradiation. (author)

Estudio de caso de un enlace de red inalambrico en una zona rural. propuesta de conexion para entidades agropecuarias

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Abiel Roche Lima

2005-07-01

Full Text Available En este trabajo se realiza el estudio de una red inalámbrica de área local WLAN que utiliza el estándar IEEE 802.11 con topología de Enlace LAN, para dar servicios de Internet a la red del Instituto de Ciencia Animal, de Cuba, que es una entidad agropecuaria ubicado en una zona rural. A través de este enlace se resuelve uno de los principales problemas que presenta el sector agropecuario, que es la falta de comunicación entre los productores, investigadores y profesores pues, de forma general, sus entidades se encuentran ubicadas en zonas carentes de infraestructura de telecomunicaciones. Para elestudio del enlace se utilizaron varios software y variables a través del protocolo SNMP (Simple Network Management Protocol, así como del software de configuración del equipo, y se definieron diferentes condiciones ambientales y de tráfico de datos. Como resultado se obtuvo que las condiciones ambientales influyen en el Indicador de ruido por subcanales de frecuencia, pero que de forma general no afecta el funcionamiento de la red, por lo que resulta viable la utilización de esta tecnología para el enlace de entidades agropecuarias en zonas rurales. Al mismo tiempo se hace referencia al uso potencial de la tecnología de comunicación por líneas eléctricas (PLC como alternativa a utilizar para la conexión de estas entidades de forma independiente o conjuntamente con las WLAN.

Algunos aspectos de la estructura de la Zona Subbética (Cordilleras Béticas. España meridional

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Hermes, Jacobus J.

1985-08-01

Full Text Available Analysis of sedimentation and tectonics of the Subbetic zone of the Betic Cordilleras leads to the conclusion that sedimentation and subsequent deformation are largely governed by a Wilson cycle (Wilson, 1966, 1968 that began the opening of the Tethyan rift in the Pangaea continent during the Pliensbachian, 180 Ma ago. The resulting ocean began to close again in the Cretaceous, a process that led to a collision between Iberia and African elements in the Burdigalian, which was followed by strike-slip movement along a shear zone between the two plates which continues to this day. It is argued that the collision led to general uplift of the Subbetic zone as shown by the termination of deep water pelagic and hemipelagic sedimentation in the entire zone, and that the subsequent strike-slip movements along a system of anastomosing faults loo to very intense deformation localized along separate fault zones, and to the opening of pull-apart basins with characteristic sedimentation sequences.

El análisis de la sedimentación y la tectónica de la Zona Subbética (Cordilleras Béticas conduce a la conclusión de que la sedimentación y la deformación posterior han sido ampliamente determinadas por un ciclo de Wilson (Wilson, 1966, 1968; Mitchell y Reading, 1978 que comenzó con la apertura del Tethys en el continente de Pangaea durante el Pliensbaquiense, hace 180 ID. a. El océano resultante empezó a cerrarse de nuevo en el Cretácico. Este proceso condujo a la colisión entre Iberia y elementos africanos en el Burdigaliense y fue seguido por un movimiento de salto en dirección a favor de una zona de cizalla que aún continúa en la actualidad. La colisión provocó el levantamiento general del la Zona Subbética, como lo demuestra el cese de la sedimentación pelágica y hemipelágica profundas por toda ella. Los movimientos subsiguientes de salto en 'dirección a favor de un sistema de fallas anastomosadas produjeron una deformación muy

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.

Science.gov (United States)

Carballeira, Néstor M; Cartagena, Michelle; Sanabria, David; Tasdemir, Deniz; Prada, Christopher F; Reguera, Rosa M; Balaña-Fouce, Rafael

2012-10-01

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7μM. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1μM) and Trypanosoma brucei rhodesiense (IC(50)=64.5μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metas de socialización maternas: relación con edad, formación académica y zona habitacional

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Jorge Mario Jaramillo

2013-10-01

Full Text Available En este artículo analizamos como la zona de vivienda (rural/urbana, el nivel de formación académica y la edad de las madres se relacionan con sus metas de socialización. Por medio de una entrevista individual estructurada pedimos a 163 madres de la ciudad de Bogotá y varios municipios de la zona rural cundiboyacense hacer una estimación del valor atribuido a distintas metas en la socialización de sus hijos e hijas de edades entre 3 y 4 años y medio. Con esto buscábamos identificar los valores prioritarios que orientan a las madres en las prácticas educativas con sus hijos. Los resultados sugieren que las madres de zonas urbanas, menor edad y mayor nivel de formación académica, se inclinan a dar mayor valor a metas de socialización relacionadas con el fomento de la independencia, mientras que las madres de mayor edad y menor nivel académico valoran más las metas de socialización vinculadas a la interdependencia. Se plantean interrogantes sobre cómo la expansión de la economía de mercado y el desarrollo de nuevas tecnologías de la comunicación podrían estar contribuyendo a cambios en los valores que inspiran las prácticas educativas maternas.

Diethyl 2-(Phenylcarbamoylphenyl Phosphorothioates: Synthesis, Antimycobacterial Activity and Cholinesterase Inhibition

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Jarmila Vinšová

2014-05-01

Full Text Available A new series of 27 diethyl 2-(phenylcarbamoylphenyl phosphorothioates (thiophosphates was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenylcarbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 µM. The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethylphenyl]carbamoyl}-phenyl O,O-diethyl phosphorothioate with MIC values from 16 µM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition and comparable (for BChE inhibition activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 µM range.

Diagnóstico del potencial turístico en las comunidades kichwas asentadas en la zona de amortiguamiento de la reserva ecológica Cotacachi Cayapas.

OpenAIRE

Flores Endara, Apauki Katari

2016-01-01

Determinar el potencial turístico en las comunidades kichwas ubicadas en la Zona de Amortiguamiento de la RECC. Son siete comunidades kichwas ubicadas en la Zona de Amortiguamiento de la Reserva Ecológica Cotacachi Cayapas, tienen recursos turísticos y al estar en un sitio estratégico cerca la Laguna de Cuicocha, se convierte en un potencial para el desarrollo del turismo comunitario. No obstante por el desconocimiento del valor turístico de los habitantes y por entidades tanto públicas y ...

Los archivos notariales como fuente histórica:una visión desde la zona bananera del Magdalena

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Adriana Mercedes Corso

2004-01-01

Full Text Available Este artículo es una exploración metodológica e historiográfica de los registrosnotariales y surge de nuestro estudio en curso de la zona bananera delMagdalena desde 1890 hasta 1930. Nuestro propósito es alertar a los estudiantesde historia sobre algunas

MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma

Science.gov (United States)

Ranjan, Atul; Iyer, Swathi V.; Ward, Christopher; Link, Tim; Diaz, Francisco J.; Dhar, Animesh; Tawfik, Ossama W.; Weinman, Steven A.; Azuma, Yoshiaki; Izumi, Tadahide; Iwakuma, Tomoo

2018-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation of Elk-1 and decreases mRNA expression of Elk-1 target genes. Reduced Elk-1 activity is caused by inhibited nuclear translocation of phosphorylated Erk1/2 (p-Erk) by MTBP and subsequent inhibition of Elk-1 phosphorylation. We also reveal that MTBP inhibits the interaction of p-Erk with importin-7/RanBP7 (IPO7), an importin family member which shuttles p-Erk into the nucleus, by binding to IPO7. Moreover, high levels of MTBP in human HCC tissues are correlated with cytoplasmic localization of p-Erk1/2. Our study suggests that MTBP suppresses metastasis, at least partially, by down-modulating the Erk1/2-Elk-1 signaling pathway, thus identifying a novel regulatory mechanism of HCC metastasis by regulating the subcellular localization of p-Erk. PMID:29765550

Inhibition of early T cell cytokine production by arsenic trioxide occurs independently of Nrf2.

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Kelly R VanDenBerg

Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is a stress-activated transcription factor that induces a variety of cytoprotective genes. Nrf2 also mediates immunosuppressive effects in multiple inflammatory models. Upon activation, Nrf2 dissociates from its repressor protein, Keap1, and translocates to the nucleus where it induces Nrf2 target genes. The Nrf2-Keap1 interaction is disrupted by the environmental toxicant and chemotherapeutic agent arsenic trioxide (ATO. The purpose of the present study was to determine the effects of ATO on early events of T cell activation and the role of Nrf2 in those effects. The Nrf2 target genes Hmox-1, Nqo-1, and Gclc were all upregulated by ATO (1-2 μM in splenocytes derived from wild-type, but not Nrf2-null, mice, suggesting that Nrf2 is activated by ATO in splenocytes. ATO also inhibited IFNγ, IL-2, and GM-CSF mRNA and protein production in wild-type splenocytes activated with the T cell activator, anti-CD3/anti-CD28. However, ATO also decreased production of these cytokines in activated splenocytes from Nrf2-null mice, suggesting the inhibition is independent of Nrf2. Interestingly, ATO inhibited TNFα protein secretion, but not mRNA expression, in activated splenocytes suggesting the inhibition is due to post-transcriptional modification. In addition, c-Fos DNA binding was significantly diminished by ATO in wild-type and Nrf2-null splenocytes activated with anti-CD3/anti-CD28, consistent with the observed inhibition of cytokine production by ATO. Collectively, this study suggests that although ATO activates Nrf2 in splenocytes, inhibition of early T cell cytokine production by ATO occurs independently of Nrf2 and may instead be due to impaired AP-1 DNA binding.

Why Do SGLT2 inhibitors inhibit only 30-50% of renal glucose reabsorption in humans?

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Liu, Jiwen Jim; Lee, TaeWeon; DeFronzo, Ralph A

2012-09-01

Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30-50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible.

Observaciones adicinales sobre la biogeografía de la zona de AmotapeHuancabamba en el norte del Perú: definiendo el límite suroriental

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Maximilian Weigend

2013-06-01

Full Text Available Observaciones de Loasaceae y Ribes (Grossulariaceae obtenidos durante estudios de campo en el Perú nos permiten definir el límite suroriental de la zona Amotape Huancabamba con gran precisión. El límite se encuentra entre la zona directamente al NE de Otuzco (departamento La Libertad, prov. Otuzco, sistema Río Chicama: 07° 50,315´ S, 078° 29,076´ W hacía el abra entre Parcoy y Buldibuyo (departamento La Libertad, provincia Pataz, N del Río Cajas: 08° 04,619´ S, 077° 25,457´ O. Los grupos de plantas típicas de la zona Amotape Huancabamba (grupo N. triphylla, N. ser. Alatae, grupo Ribes andicola, Nasa picta subsp. picta tienen sus límites suroriental de distribución en el Norte de la provincia de Pataz (La Libertad, y se encuentran reemplazadas por grupos de los Andes Centrales (grupo N. poissoniana, Ribes viscosum inmediatamente al sur de esta abra.

Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway

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Zeng, Xiao-Qing, E-mail: zeng.xiaoqing@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Na, E-mail: Linala.2009@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Pan, Du-Yi, E-mail: lasikesmi@hotmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Miao, Qing, E-mail: sadsadvenus@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Gui-Fen, E-mail: ma.guifen@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Liu, Yi-Mei, E-mail: liuyimei1988@163.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Tseng, Yu-Jen, E-mail: dianatseng14@gmail.com [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Li, Feng, E-mail: li.feng2@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Xu, Li-Li, E-mail: xu.lili3@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: chen.shiyao@zs-hospital.sh.cn [Department of Gastroenterology of Zhongshan Hospital, Fudan University, Shanghai (China); Institute of Endoscopic Research of Zhongshan Hospital, Fudan University, Shanghai (China)

2015-09-04

Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its precise role in hepatic angiogenesis induced by liver sinusoidal endothelial cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2 on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured human LSECs were infected with different lentiviruses to overexpress or suppress KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation test, were used to investigate the roles of KLF2 in the proliferation, migration and vessel tube formation of LSECs, respectively. The expression and phosphorylation of ERK1/2 were detected by western blot. We discovered that the up-regulation of KLF2 expression dramatically inhibited proliferation, migration and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2 expression significantly promoted proliferation, migration and tube formation in treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2 pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted. In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of cell proliferation, migration, and vessel tube formation. These functions of KLF2 may be mediated through the ERK1/2 signaling pathway. - Highlights: • Overexpression of KLF2 inhibits the proliferation and migration of LSECs. • Overexpression of KLF2 inhibits the angiogenesis of LSECs. • ERK1/2 signaling pathway involved in the anti-angiogenic process of KLF2 on LSECs.

A Flexure-Guided Piezo Drill for Penetrating the Zona Pellucida of Mammalian Oocytes.

Science.gov (United States)

Johnson, Wesley; Dai, Changsheng; Liu, Jun; Wang, Xian; Luu, Devin K; Zhang, Zhuoran; Ru, Changhai; Zhou, Chao; Tan, Min; Pu, Huayan; Xie, Shaorong; Peng, Yan; Luo, Jun; Sun, Yu

2018-03-01

Mammalian oocytes such as mouse oocytes have a highly elastic outer membrane, zona pellucida (ZP) that cannot be penetrated without significantly deforming the oocyte, even with a sharp micropipette. Piezo drill devices leverage lateral and axial vibration of the micropipette to accomplish ZP penetration with greatly reduced oocyte deformation. However, existing piezo drills all rely on a large lateral micropipette vibration amplitude ( 20 ) and a small axial vibration amplitude (0.1 ). The very large lateral vibration amplitude has been deemed to be necessary for ZP penetration although it also induces larger oocyte deformation and more oocyte damage. This paper reports on a new piezo drill device that uses a flexure guidance mechanism and a systematically designed pulse train with an appropriate base frequency. Both simulation and experimental results demonstrate that a small lateral vibration amplitude (e.g., 2 ) and an axial vibration amplitude as large as 1.2 were achieved. Besides achieving 100% effectiveness in the penetration of mouse oocytes (n = 45), the new piezo device during ZP penetration induced a small oocyte deformation of 3.4 versus larger than 10 using existing piezo drill devices.

WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

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Xiangshu Xian

2016-11-01

Full Text Available Background: Cannabinoids (the active components of Cannabis sativa and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN was associated with gastric cancer (GC metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2 expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

Physical activity and cardiovascular risk factors among rural and urban groups and rural-to-urban migrants in Peru: a cross-sectional study Actividad física y factores de riesgo de enfermedades cardiovasculares en grupos rurales y urbanos y en migrantes de zonas rurales a urbanas en Perú: estudio transversal

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Ruth M. Masterson Creber

2010-07-01

Full Text Available OBJECTIVE: To compare physical activity and sedentary behavior patterns of rural-to-urban migrants in Peru versus lifetime rural and urban residents and to determine any associations between low physical activity and four cardiovascular risk factors: obesity (body mass index > 30 kg/m², systolic and diastolic blood pressure, hypertension, and metabolic syndrome. METHODS: The PERU MIGRANT (PEru's Rural to Urban MIGRANTs cross-sectional study was designed to measure physical activity among rural, urban, and rural-to-urban migrants with the International Physical Activity Questionnaire (IPAQ. RESULTS: The World Health Organization (WHO age-standardized prevalence of low physical activity was 2.2% in lifetime rural residents, 32.2% in rural-to-urban migrants, and 39.2% in lifetime urban residents. The adjusted odds ratios for low physical activity were 21.43 and 32.98 for migrant and urban groups respectively compared to the rural group. The adjusted odds ratio for being obese was 1.94 for those with low physical activity. There was no evidence of an association between low physical activity and blood pressure levels, hypertension, or metabolic syndrome. CONCLUSIONS: People living in a rural area had much higher levels of physical activity and lower risk of being overweight and obese compared to those living in an urban area of Lima. Study participants from the same rural area who had migrated to Lima had levels of physical inactivity and obesity similar to those who had always lived in Lima. Interventions aimed at maintaining higher levels of physical activity among rural-to-urban migrants may help reduce the epidemic of obesity in urban cities.OBJETIVO: Comparar los patrones de actividad física y de comportamiento sedentario de migrantes de zonas rurales a urbanas del Perú con los patrones de habitantes permanentes de zonas rurales y urbanas, e identificar cualquier asociación entre el bajo nivel de actividad física y cuatro factores de

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

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Lättig, Jens; Böhl, Markus; Fischer, Petra; Tischer, Sandra; Tietböhl, Claudia; Menschikowski, Mario; Gutzeit, Herwig O.; Metz, Peter; Pisabarro, M. Teresa

2007-08-01

The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

International Nuclear Information System (INIS)

Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-01-01

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Lamy, Sylvie, E-mail: lamy.sylvie@uqam.ca; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-03-10

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation.

Science.gov (United States)

Zhang, Xiaobing; van den Pol, Anthony N

2017-05-26

The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons. Copyright © 2017, American Association for the Advancement of Science.

Synergistic effect of halide ions on the corrosion inhibition of aluminium in H{sub 2}SO{sub 4} using 2-acetylphenothiazine

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Ebenso, E.E

2003-03-05

The corrosion inhibition of aluminium in H{sub 2}SO{sub 4} in the presence of 2-acetylphenothiazine (2APTZ) at temperature range of 30-60 deg. C was studied using the weight loss and thermometric techniques. The effect of addition of halides (KCl, KBr, KI) is also reported. The inhibition efficiency (I, %) increased with increase in concentration of 2APTZ. The addition of the halides increased the inhibition efficiency to a considerable extent. The temperature increased the corrosion rate and inhibition efficiency in the range 30-60 deg. C in the absence and presence of the inhibitor and halides. Phenomenon of chemical adsorption is proposed. Flory-Huggins adsorption isotherm equation was obeyed at all the concentrations studied. The decrease in inhibition efficiency (and surface coverage values) was found to be in the order I{sup -}>Br{sup -}>Cl{sup -} which clearly indicates that the radii and the electronegativity of halides play a significant role in the adsorption process. All the data acquired reveal that 2APTZ acts as an inhibitor in the acid environment from the two techniques used. The synergistic effect of 2APTZ and halide ions is discussed.

Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

Science.gov (United States)

Jiang, Quan; Lian, Anji; He, Qi

2016-07-01

Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of ZP1 gene reveals differences in zona pellucida composition in carnivores.

Science.gov (United States)

Moros-Nicolás, C; Leza, A; Chevret, P; Guillén-Martínez, A; González-Brusi, L; Boué, F; Lopez-Bejar, M; Ballesta, J; Avilés, M; Izquierdo-Rico, M J

2018-01-01

The zona pellucida (ZP) is an extracellular envelope that surrounds mammalian oocytes. This coat participates in the interaction between gametes, induction of the acrosome reaction, block of polyspermy and protection of the oviductal embryo. Previous studies suggested that carnivore ZP was formed by three glycoproteins (ZP2, ZP3 and ZP4), with ZP1 being a pseudogene. However, a recent study in the cat found that all four proteins were expressed. In the present study, in silico and molecular analyses were performed in several carnivores to clarify the ZP composition in this order of mammals. The in silico analysis demonstrated the presence of the ZP1 gene in five carnivores: cheetah, panda, polar bear, tiger and walrus, whereas in the Antarctic fur seal and the Weddell seal there was evidence of pseudogenisation. Molecular analysis showed the presence of four ZP transcripts in ferret ovaries (ZP1, ZP2, ZP3 and ZP4) and three in fox ovaries (ZP2, ZP3 and ZP4). Analysis of the fox ZP1 gene showed the presence of a stop codon. The results strongly suggest that all four ZP genes are expressed in most carnivores, whereas ZP1 pseudogenisation seems to have independently affected three families (Canidae, Otariidae and Phocidae) of the carnivore tree.

Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

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Dong Ju Son

2014-08-01

Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells

Science.gov (United States)

Jiao, G; Guo, W; Ren, T; Lu, Q; Sun, Y; Liang, W; Ren, C; Yang, K; Sun, K

2014-01-01

Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment. PMID:25501832

Phosphorus in agroforestry systems: a contribution to sustainable agriculture in the Zona da Mata of Minas Gerais, Brazil

NARCIS (Netherlands)

Cardoso, I.M.

2002-01-01

The Zona da Mata is a region situated in the domain of the Atlantic Coastal Rainforest in the southeast of the state of Minas Gerais, Brazil. This domain stretches along the Brazilian coast from north to south and ranks among the top five of the 25 biodiversity hotspots, the richest and the

Estado nutricional y parasitosis intestinales en niños residentes en zonas urbana, periurbana y rural del partido de Brandsen (Buenos Aires, Argentina

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Cesani Rossi, María Florencia

2007-01-01

Full Text Available El presente estudio tuvo como objeto analizar el estado nutricional y las parasitosis intestinales en niños de 3 a 6 años de edad, residentes en zonas urbanas (U, periurbanas (PU y rurales (R del partido de Brandsen. La muestra quedó constituida por 600 niños (302 varones y 298 mujeres. Los valores P85#P95 definieron sobrepeso y >P95 obesidad. Se tomaron muestras de materia fecal seriada y escobillado anal que fueron analizadas mediante técnicas de concentración por sedimentación (Ritchie y flotación (Willis. Los datos fueron asociados con las características socioambientales de cada zona. PU presentó prevalencias de baja talla para la edad y parasitosis significativamente mayores que U (p<0.01. Se registraron 7 especies parásitas en U, 8 en PU y 4 en R, siendo Enterobius vermicularis, Blastocystis hominis y Giardia lamblia las especies más abundantes. También el poliparasitismo fue mayor en PU. Aunque el sobrepeso y la obesidad fueron elevados en las tres zonas, las mayores prevalencias se registraron en PU y R respecto de U (p<0.01. La coexistencia de desnutrición y sobrepeso-obesidad, podría vincularse con los cambios experimentados en las costumbres alimentarias y los modos de vida de estas poblaciones en el contexto de la transición nutricional. La zona periurbana presenta las peores condiciones socio-ambientales para el crecimiento y la salud de los niños en edad preescolar.

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

International Nuclear Information System (INIS)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul; Han, Hyo-Kyung; Ryu, Chang Seon; Kim, Sang Kyum; Kwak, Mi Kyong; Kang, Keon Wook

2009-01-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

Inhibition of Shiga toxin 2 (Stx2) in apple juices and its resistance to pasteurization.

Science.gov (United States)

Rasooly, Reuven; Do, Paula M; Levin, Carol E; Friedman, Mendel

2010-06-01

In the present study, we evaluated Shiga toxin (Stx2) activity in apple juices by measuring a decrease in dehydrogenase activity of Vero cells with the microculture tetrazolium (MTT) assay. Freshly prepared juice from Red Delicious apples and Golden Delicious apples inhibited the biological activity of the bacterial toxin Stx2 produced by E. coli O157:H7 strains. Studies with immunomagnetic beads bearing specific antibodies against the toxin revealed that Stx2 activity was restored when removed from the apple juice. SDS gel electrophoresis revealed no difference (P pasteurize apple juice, but lost all activity when exposed to 100 degrees C for 5 min. The results suggest that pasteurization of apple juice used to inactivate E. coli O157:H7 has no effect on Stx2, and that food-compatible and safe antitoxin compounds can be used to inhibit the biological activity of the Shiga toxin.

Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

Directory of Open Access Journals (Sweden)

Mingzhu Zhuang

Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

Características del fruto de cuatro pasifloras de la zona andina venezolana

OpenAIRE

Aular, Jesús; Rodríguez, Yesenia; Roa, Sara; Iade, Patricia; Antolínez, María

2004-01-01

En la zona andina de Venezuela existen especies del género Passiflora con elevado potencial agronómico. Con el objetivo de contribuir a su conocimiento, se estudiaron las características del fruto de P. ligularis Juss, P. mollisima HBK Bailey, P. mixta L. y P. quadrangularis L. colectadas en los estados Táchira, las tres primeras especies, y Mérida, la cuarta. Se empleó un diseño estadístico completamente al azar y se determinaron características físicas y químicas de la parte comestible del ...

Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

Science.gov (United States)

Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

2012-08-01

Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

Susceptibilidad canina a rabia después de una campaña de vacunación en zonas endémicas del Perú

OpenAIRE

Ricardo López I; Albina Díaz O; Edgar Condori C

2007-01-01

Objetivo: Determinar el nivel de la respuesta inmune posterior a una campaña de vacunación antirrábica canina en dos zonas que han presentado en los últimos años casos de rabia canina. Materiales y métodos: Se realizó una encuesta serológica, en 101 y 199 canes localizados en los distritos de Tambo Grande (Piura) y Juliaca (Puno) respectivamente y se efectuó la prueba del seroneutralización en ratón para determinar la proporción de canes con anticuerpos protectores (¡Ý 0,5 UI/mL) según zona d...

Avifauna da Zona da Mata de Minas Gerais: municípios de Goianá e Rio Novo, com alguns registros para Coronel Pacheco e Juiz de Fora Avifaunal inventory of the "Zona da Mata" of Minas Gerais: Goianá and Rio Novo, with some records for Coronel Pacheco and Juiz de Fora municipalities

Directory of Open Access Journals (Sweden)

Rômulo Ribon

2004-04-01

Full Text Available A partir da oportunidade criada pelos Estudos de Impacto Ambiental para implantação do Aeroporto Regional da Zona da Mata, fez-se a caracterização qualitativa preliminar da avifauna dos municípios de Goianá e Rio Novo, na Zona da Mata, sudeste de Minas Gerais. Alguns registros para áreas limítrofes dos municípios de Juiz de Fora e Coronel Pacheco são também fornecidos. A região, originalmente coberta por Mata Atlântica, é hoje composta por um mosaico de pastagens, fragmentos florestais, pomares domésticos e ambientes limícolas. Foram registradas 185 espécies de aves, sendo os ambientes de mata os mais ricos em espécies. Neste artigo serão dadas informações sobre o habitat, o método de registro das espécies e, para algumas delas, sobre a atividade reprodutiva. A presença da planície de inundação do rio Novo proporciona ambiente para espécies normalmente pouco abundantes no restante da Zona da Mata. Destacam-se a extinção local de pelo menos duas espécies registradas no século XIX, a presença de algumas aves ameaçadas de extinção e a importância de estudos de impacto ambiental como oportunidade, muitas vezes perdida, para obtenção de informações biológicas.The support provided by the Environmental Impact Assessment for the construction of the Zona da Mata Regional Airport allowed the conduction of a qualitative sampling of the bird community at Goianá and Rio Novo municipalities, in the "Zona da Mata" region, southeastern Minas Gerais, Brazil. Some records for neighboring areas at Juiz de Fora and Coronel Pacheco municipalities are also given. The region is located in the Semidecidual Lowland Atlantic Forest domain but the current landscape is a mosaic of artificial pasturelands, secondary forest fragments, small orchards around farms' headquarters, small ponds for fish farming, and marshes at the Rio Novo floodplain. We recorded 185 bird species with the forest fragments being the richest habitat

Zona Hambat Ekstrak Daun Sirih Merah Terhadap Staphylococcus Aureus Dan Candida Albicans Diisolasi Dari Denture Stomatitis

OpenAIRE

Veronika, lara

2017-01-01

Zona Hambat Ekstrak Daun Sirih Merah terhadap Staphylococcus aureus dan Candida albicans diisolasi dari denture stomatitis xi + 43 halaman Ekstrak daun sirih merah merupakan salah satu obat tradisional yang saat ini banyak digunakan masyarakat Indonesia. Ekstrak daun sirih merah ini dapat menghambat pertumbuhan bakteri dan jamur disebabkan karena adanya senyawa alkaloid, flavonoid, polifenol, tanin dan minyak atsiri. Salah satu bakteri dan jamur yang dapat dihambat oleh ekstrak daun sir...

Automation and Optimization of Multipulse Laser Zona Drilling of Mouse Embryos During Embryo Biopsy.

Science.gov (United States)

Wong, Christopher Yee; Mills, James K

2017-03-01

Laser zona drilling (LZD) is a required step in many embryonic surgical procedures, for example, assisted hatching and preimplantation genetic diagnosis. LZD involves the ablation of the zona pellucida (ZP) using a laser while minimizing potentially harmful thermal effects on critical internal cell structures. Develop a method for the automation and optimization of multipulse LZD, applied to cleavage-stage embryos. A two-stage optimization is used. The first stage uses computer vision algorithms to identify embryonic structures and determines the optimal ablation zone farthest away from critical structures such as blastomeres. The second stage combines a genetic algorithm with a previously reported thermal analysis of LZD to optimize the combination of laser pulse locations and pulse durations. The goal is to minimize the peak temperature experienced by the blastomeres while creating the desired opening in the ZP. A proof of concept of the proposed LZD automation and optimization method is demonstrated through experiments on mouse embryos with positive results, as adequately sized openings are created. Automation of LZD is feasible and is a viable step toward the automation of embryo biopsy procedures. LZD is a common but delicate procedure performed by human operators using subjective methods to gauge proper LZD procedure. Automation of LZD removes human error to increase the success rate of LZD. Although the proposed methods are developed for cleavage-stage embryos, the same methods may be applied to most types LZD procedures, embryos at different developmental stages, or nonembryonic cells.

Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

DEFF Research Database (Denmark)

Hein, Jamin B; Nilsson, Jakob

2016-01-01

Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during...... this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2......, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation...

Susceptibilidad dE Lutzomyia verrucarrum a piretroides en zonas endémicas de Enfermedad de Carrión de Ancash

Directory of Open Access Journals (Sweden)

Jorge Lucero

2008-04-01

Full Text Available La enfermedad de Carrión es una infección metaxénica endémica del Perú, el control vectorial de la Lutzomyia verrucarum con insecticidas es una de las formas más usadas para reducir su morbilidad. Se determinó la susceptibilidad de este vector a los piretroides más usados (cyflutrina, alfacipermetrina y deltametrina en dos zonas endémicas altoandinas de Ancash (Llumpa: 3200 msnm y Maya: 2600 msnm, Perú en junio de 1999. Se expuso a 50 mosquitos por cada zona e insecticida usando la prueba de contacto para anophelinos modificada. Se encontró una mortalidad del 100% para cada piretroide ensayado. Si bien se demostró una susceptibilidad total de L. verrucarum es necesario implementar la vigilancia de la resistencia a insecticidas como se hace con otros vectores en el Perú.

Migrantes indígenas en la zona metropolitana de monterrey y los procesos de adaptación - INDIGENOUS MIGRANTS IN MONTERREY METROPOLITAN REGION AND THEIR PROCESS OF ADAPTION

Directory of Open Access Journals (Sweden)

Arun Kumar Acharya

2010-11-01

Full Text Available En México, un fenómeno notable es la migración del campo a la ciudad. En los últimos años se ha dado un crecimiento en el número de migrantes indígenas hacia las ciudades del norte del país, específicamente a la Zona Metropolitana de Monterrey (ZMM en busca de empleo. Al llegar a esta metrópoli, los migrantes tienen problemas para adaptarse e integrarse en el ámbito urbano de esta sociedad, fundamentalmente por la oculta discriminación existente hacia los indígenas, por lo cual, muchos de ellos llegan a sufrir problemas sociales, psicológicos y personales, que provocan el retorno de algunos a sus lugares de origen o el cambio de residencia. En este sentido, en el presente artículo se ha investigado la importancia de la migración indígena hacia la Zona Metropolitana de Monterrey y sus procesos de integración y adaptación. El análisis se basó en los resultados de una encuesta aplicada a estos migrantes en los primeros meses del 2008 en esta zona urbana. Palabra claves: Migración Indígena, Proceso de adaptación, Discriminación, y Zona Metropolitana de Monterrey.

Variabilidad espacial y temporal de la temperatura del aire en la zona cafetera colombiana

OpenAIRE

Edna Paola Pérez Rendón; Víctor Hugo Ramírez Builes; Andrés Javier Peña Quiñones

2016-01-01

La zona cafetera colombiana está ubicada en- teramente en el hemisferio norte, entre los 1 y 11° grados de latitud, sobre la cordillera de los Andes. Esta condición (ecuatorial andina) ha hecho que se dé por sentado que la variación temporal de la temperatura es mínima y que por ello, en su mayor parte la variabilidad de este elemento es es- pacial, atribuible casi exclusivamente a los cambios en altura sobre el nivel del mar. En este estudio se exploran factores de variación al...

Dieta de Phyllodactyllus reissi (Sauria:Gekkonidae) en la Zona Reservada de Tumbes, Perú

OpenAIRE

Jordán, Juan C.

2006-01-01

The purpose of this paper is to describe the diet of Phyllodactylus reissi, a nocturnal common gecko distributed from southern Ecuador to central Perú. A total of 15 individuals were captured inside buildings at Quebrada Faical, El Caucho and Bocana Murciélago in the Zona Reservada de Tumbes. Coleoptera and Blattoptera were the dominant preys from a total of six prey types found in stomachs. The number of prey per stomach were between 1 to 9, with 3 preys in average; the prey length average w...

Aspectos geopolíticos en el desarrollo de la zona franca industrial de Ilo

OpenAIRE

Cardenas Nuñez, Gilberto; Cardenas Nuñez, Gilberto

1994-01-01

El presente trabajo de Tesis enfatiza el aspecto geopolítico en el desarrollo de la Zona franca Industrial de Ilo (ZOFRI-IL0). La razón de tal énfasis es simple: por este aspecto específicamente es que se creó la ZOFRI-ILO. En consecuencia, el tratamiento del tema tiene que ver con la influencia geopolítica en las sucesivas etapas de su desarrollo, considerando sus posibilidades de desarrollo a futuro en el marco de las tendencias internacionales de la globalización de la economía mundial. ...

Detection and evaluation of corrosion zones at high temperature in steam generators; Deteccion y evaluacion de zonas de corrosion en alta temperatura de generadoras de vapor

Energy Technology Data Exchange (ETDEWEB)

Martinez Villafane, Alberto; Chacon Nava, Jose G; Huerta Espino, Mario; Mojica Calderon, Cecilio; Castillo Viveros, Antonio [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

1991-12-31

This paper presents the methodology for the detection and evaluation of high corrosion zones at high temperature. The results found up to now, show a critical zone in the Babcock Hitachi design, specifically in the high temperature reheater in the zone nearby the outlet header. In the normalized design CE (Mitsubishi) of 300 MW and CE (Canada) of 300 MW, the results found in recent years show small thickness reduction, therefore a good operation of these steam generators is recognized. [Espanol] En este trabajo se presenta la metodologia para la deteccion y evaluacion de zonas de corrosion en alta temperatura. Los resultados encontrados hasta el momento muestran una zona critica en el diseno Babcock Hitachi, especificamente en el recalentador de alta temperatura en la zona cercana al cabezal de salida. En el diseno normalizado CE (Mitsubishi) de 300 MW y CE (Canada) de 300 MW, los resultados encontrados en anos recientes muestran poca disminucion de espesor, por lo que se considera una buena operacion de estos generadores de vapor.

Detection and evaluation of corrosion zones at high temperature in steam generators; Deteccion y evaluacion de zonas de corrosion en alta temperatura de generadoras de vapor

Energy Technology Data Exchange (ETDEWEB)

Martinez Villafane, Alberto; Chacon Nava, Jose G.; Huerta Espino, Mario; Mojica Calderon, Cecilio; Castillo Viveros, Antonio [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

1990-12-31

This paper presents the methodology for the detection and evaluation of high corrosion zones at high temperature. The results found up to now, show a critical zone in the Babcock Hitachi design, specifically in the high temperature reheater in the zone nearby the outlet header. In the normalized design CE (Mitsubishi) of 300 MW and CE (Canada) of 300 MW, the results found in recent years show small thickness reduction, therefore a good operation of these steam generators is recognized. [Espanol] En este trabajo se presenta la metodologia para la deteccion y evaluacion de zonas de corrosion en alta temperatura. Los resultados encontrados hasta el momento muestran una zona critica en el diseno Babcock Hitachi, especificamente en el recalentador de alta temperatura en la zona cercana al cabezal de salida. En el diseno normalizado CE (Mitsubishi) de 300 MW y CE (Canada) de 300 MW, los resultados encontrados en anos recientes muestran poca disminucion de espesor, por lo que se considera una buena operacion de estos generadores de vapor.

Incentivos para atraer y retener personal de salud de zonas rurales del Perú: un estudio cualitativo

Science.gov (United States)

Huicho, Luis; Canseco, Francisco Díez; Lema, Claudia; Miranda, J. Jaime; Lescano, Andrés G.

2014-01-01

El objetivo fue identificar incentivos de atracción y retención en zonas rurales y distantes de Ayacucho, Perú. Fueron realizadas entrevistas en profundidad con 80 médicos, enfermeras, obstetras y técnicos (20 por grupo) de las zonas más pobres y con 11 funcionarios. No existen políticas sistemáticas de atracción y retención de personal de salud en Ayacucho. Los principales incentivos, en orden de importancia, fueron mejoras salariales, oportunidades de formación y capacitación, estabilidad laboral y nombramiento, mejoras en infraestructura y equipos, e incremento del personal. Se mencionaron también mejoras en la vivienda y alimentación, mayor cercanía con la familia y reconocimiento por el sistema de salud. Existen coincidencias y singularidades entre los distintos grupos sobre los incentivos clave para estimular el trabajo rural, que deben considerarse al diseñar políticas públicas. Las iniciativas del Estado deben comprender procesos rigurosos de monitoreo y evaluación, para asegurar que las mismas tengan el impacto deseado. PMID:22488318

Silencing Nrf2 impairs glioma cell proliferation via AMPK-activated mTOR inhibition

Energy Technology Data Exchange (ETDEWEB)

Jia, Yue [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wang, Handong, E-mail: njhdwang@hotmail.com [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wang, Qiang [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Ding, Hui [Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wu, Heming [Department of Neurosurgery, Nanjing Jingdu Hospital, No. 34, Biao 34, Yanggongjing Road, Nanjing 210002, Jiangsu Province (China); Pan, Hao [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China)

2016-01-15

Gliomas are the leading cause of death among adults with primary brain malignancies. Treatment for malignant gliomas remains limited, and targeted therapies have been incompletely explored. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription regulator for antioxidant and detoxification enzymes, is abundantly expressed in cancer cells. In this study, the role and mechanism of Nrf2 in cancer cell proliferation was investigated in multiple glioma cell lines. We first evaluated the expression patterns of Nrf2 in four glioma cell lines and found all four cell lines expressed Nrf2, but the highest level was observed in U251 cells. We further evaluated the biological functions of Nrf2 in U251 glioma cell proliferation by specific inhibition of Nrf2 using short hairpin RNA (shRNA). We found that Nrf2 depletion inhibited glioma cell proliferation. Nrf2 depletion also decreased colony formation in U251 cells stably expressing Nrf2 shRNA compared to scrambled control shRNA. Moreover, suppression of Nrf2 expression could lead to ATP depletion (with concomitant rise in AMP/ATP ratio) and consequently to AMPK-activated mTOR inhibition. Finally, activation of adenosine monophosphate–activated protein kinase (AMPK) by treated with phenformin, an AMPK agonist, can mimic the inhibitory effect of Nrf2 knockdown in U251 cells. In conclusion, our findings will shed light to the role and mechanism of Nrf2 in regulating glioma proliferation via ATP-depletion-induced AMPK activation and consequent mTOR inhibition, a novel insight into our understanding the role and mechanism of Nrf2 in glioma pathoetiology. To our knowledge, this is also the first report to provide a rationale for the implication of cross-linking between Nrf2 and mTOR signaling.

Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

Directory of Open Access Journals (Sweden)

Shin-ichi Kawaguchi

2018-04-01

Full Text Available Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1 has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2c cells by measuring HIF response element (HRE promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

Slit2 inactivates GSK3β to signal neurite outgrowth inhibition.

Directory of Open Access Journals (Sweden)

Justin Byun

Full Text Available Slit molecules comprise one of the four canonical families of axon guidance cues that steer the growth cone in the developing nervous system. Apart from their role in axon pathfinding, emerging lines of evidence suggest that a wide range of cellular processes are regulated by Slit, ranging from branch formation and fasciculation during neurite outgrowth to tumor progression and to angiogenesis. However, the molecular and cellular mechanisms downstream of Slit remain largely unknown, in part, because of a lack of a readily manipulatable system that produces easily identifiable traits in response to Slit. The present study demonstrates the feasibility of using the cell line CAD as an assay system to dissect the signaling pathways triggered by Slit. Here, we show that CAD cells express receptors for Slit (Robo1 and Robo2 and that CAD cells respond to nanomolar concentrations of Slit2 by markedly decelerating the rate of process extension. Using this system, we reveal that Slit2 inactivates GSK3β and that inhibition of GSK3β is required for Slit2 to inhibit process outgrowth. Furthermore, we show that Slit2 induces GSK3β phosphorylation and inhibits neurite outgrowth in adult dorsal root ganglion neurons, validating Slit2 signaling in primary neurons. Given that CAD cells can be conveniently manipulated using standard molecular biological methods and that the process extension phenotype regulated by Slit2 can be readily traced and quantified, the use of a cell line CAD will facilitate the identification of downstream effectors and elucidation of signaling cascade triggered by Slit.

Análisis de los determinantes socioeconómicos del gasto de bolsillo en medicamentos en seis zonas geográficas de Panamá.

Science.gov (United States)

Herrera-Ballesteros, Victor H; Castro, Franz; Gómez, Beatriz

2018-04-27

Caracterizar el gasto de bolsillo privado en medicamentos en función de los determinantes sociodemográficos y socioeconómicos. MATERIALES Y MéTODOS: La fuente de datos es la Encuesta de Gasto de Bolsillo en Medicamentos de 2014. Se caracterizó el gasto de bolsillo privado mediante variables explicativas sociodemográficas (SOD) y socioeconómicas (SES). Se hizo análisis factorial por componentes principales, regresión logística y lineal simple. Los Odds Ratio demuestran que la educación y la zona geográfica son determinantes fundamentales que inciden en el gasto de bolsillo. Los medicamentos son productos necesarios, en adición a que el gasto de bolsillo aumenta a un promedio del 2% por cada año de vida cronológica adicional. Existe mayor vulnerabilidad en las zonas más pauperizadas respecto del acceso a medicamentos, en especial en las indígenas e implica un mayor riesgo de gasto catastrófico a menor ingreso ante la mayor prevalencia de enfermedades crónicas. Copyright © 2018. Published by Elsevier Inc.

TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.

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Sarah A Benson

2009-07-01

Full Text Available Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3CSK(4 and assayed responses to IFN-gamma. Pam(3CSK(4 stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.

Inhibition of PKR protects against H2O2-induced injury on neonatal cardiac myocytes by attenuating apoptosis and inflammation.

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Wang, Yongyi; Men, Min; Xie, Bo; Shan, Jianggui; Wang, Chengxi; Liu, Jidong; Zheng, Hui; Yang, Wengang; Xue, Song; Guo, Changfa

2016-12-08

Reactive oxygenation species (ROS) generated from reperfusion results in cardiac injury through apoptosis and inflammation, while PKR has the ability to promote apoptosis and inflammation. The aim of the study was to investigate whether PKR is involved in hydrogen peroxide (H 2 O 2 ) induced neonatal cardiac myocytes (NCM) injury. In our study, NCM, when exposed to H 2 O 2 , resulted in persistent activation of PKR due to NCM endogenous RNA. Inhibition of PKR by 2-aminopurine (2-AP) or siRNA protected against H 2 O 2 induced apoptosis and injury. To elucidate the mechanism, we revealed that inhibition of PKR alleviated H 2 O 2 induced apoptosis companied by decreased caspase3/7 activity, BAX and caspase-3 expression. We also revealed that inhibition of PKR suppressed H 2 O 2 induced NFκB pathway and NLRP3 activation. Finally, we found ADAR1 mRNA and protein expression were both induced after H 2 O 2 treatment through STAT-2 dependent pathway. By gain and loss of ADAR1 expression, we confirmed ADAR1 modulated PKR activity. Therefore, we concluded inhibition of PKR protected against H 2 O 2 -induced injury by attenuating apoptosis and inflammation. A self-preservation mechanism existed in NCM that ADAR1 expression is induced by H 2 O 2 to limit PKR activation simultaneously. These findings identify a novel role for PKR/ADAR1 in myocardial reperfusion injury.

Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro

International Nuclear Information System (INIS)

Wang, Anxun; Zhang, Bin; Huang, Hongzhang; Zhang, Leitao; Zeng, Donglin; Tao, Qian; Wang, Jianguang; Pan, Chaobin

2008-01-01

Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas. Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels. Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma. These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research

Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition.

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Harrison, Ian F; Smith, Andrew D; Dexter, David T

2018-02-14

Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of

Cátalogo de epífitas vasculares del sector El Silencio (Parque Nacional Natural Paramillo y zona amortiguadora, Córdoba, Colombia

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Rosalba Ruiz Vega

2015-09-01

Full Text Available Se presenta el catálogo de la vegetación epifita vascular de un sector del Parque Nacional Natural Paramillo (PNNP y zona amortiguadora (Córdoba, Colombia. Se realizaron muestreos en un área de 0,1 hectárea, donde se colectaron todas las epífitas vasculares distribuidas en los forófitos que presentaron un DAP ≥2,5 cm en cuatro sectores, El Silencio (interior del PNNP, Tuis Tuis, Tuis Tuis Arriba y Alto de Chibogadó (zona amortiguadora, correspondientes al bosque húmedo tropical (Bh-T en el municipio de Tierralta. Se encontraron 2504 individuos de epífitas vasculares. El catálogo contiene 73 especies distribuidas en 41 géneros y 18 familias. El sector Tuis Tuis presentó el mayor número de especies (33. Las familias mejor representadas corresponden a las Araceae, Bromeliaceae y Orchidaceae, destacándose por mayor número de especies y géneros la familia Orchidaceae (20/15. Los géneros más diversos fueron Anthurium con ocho especies, Guzmania seis, Tillandsia y Aechmea con cinco cada uno. Los helechos reúnen solo el 6 % de la flora epifita. Se reportan  nuevos registros de especies para el departamento de Córdoba (39, ampliando el rango de distribución de este grupo de plantas en el país.

Delimitación de zonas federales y áreas de amortiguamiento en ríos afectados por el crecimiento urbano como estrategia para prevenir inundaciones

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Adrián Leonardo Ferriño Fierro

2015-12-01

Full Text Available En la actualidad, debido al crecimiento de las zonas urbanas y la ocupación de las márgenes de los ríos en las ciudades, vivimos en constante riesgo, invirtiendo enormes cantidades de recursos económicos en reconstrucciones y apoyo a damnificados por las inundaciones. Si bien las inundaciones son eventos naturales que se presentan en todo el mundo, sus consecuencias pueden variar según características de desarrollo histórico, socioeconómicas y culturales de las ciudades, y del respeto de las áreas hidráulicas y zonas de amortiguamiento de sus corrientes de agua. En la presente investigación, se desarrolló una propuesta para determinar áreas de amortiguamiento en ríos afectados por el crecimiento urbano para prevenir inundaciones, basada en aspectos técnicos, legales y ambientales. El caso de estudio fue el río Pesquería dentro de la zona metropolitana de Monterrey al cruzar por los municipios de García, Monterrey, General Escobedo, Apodaca, y Pesquería, Nuevo León.

Pharmacological inhibition of arachidonate 15-lipoxygenase (ALOX15) protects human spermatozoa against oxidative stress.

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Walters, Jessica L H; De Iuliis, Geoffry N; Dun, Matthew D; Aitken, Robert John; McLaughlin, Eileen A; Nixon, Brett; Bromfield, Elizabeth G

2018-03-13

One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15). Although ALOX15 has yet to be characterized in human spermatozoa, our previous studies have revealed a strong link between ALOX15 activity and the levels of oxidative stress and 4HNE in mouse germ cell models. In view of these data, we sought to assess the function of ALOX15 in mature human spermatozoa and determine whether the pharmacological inhibition of this enzyme could influence the level of oxidative stress experienced by these cells. By driving oxidative stress in vitro with exogenous H2O2, our data reveal that 6,11-dihydro[1]benzothiopyrano[4,3-b]indole (PD146176; a selective ALOX15 inhibitor), was able to significantly reduce several deleterious, oxidative insults in spermatozoa. Indeed, PD146176 attenuated the production of ROS, as well as membrane lipid peroxidation and 4HNE production in human spermatozoa. Accordingly, ALOX15 inhibition also protected the functional competence of these cells to acrosome react and bind homologous human zonae pellucidae. Together, these results implicate ALOX15 in the propagation of an oxidative stress cascade within human spermatozoa and offer insight into potential therapeutic avenues to address male fertility that arises from oxidative stress.

Antioxidants Inhibit Formation of 3-Monochloropropane-1,2-diol Esters in Model Reactions.

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Li, Chang; Jia, Hanbing; Shen, Mingyue; Wang, Yuting; Nie, Shaoping; Chen, Yi; Zhou, Yongqiang; Wang, Yuanxing; Xie, Mingyong

2015-11-11

The capacities of six antioxidants to inhibit the formation of 3-monochloropropane-1,2 diol (3-MCPD) esters were examined in this study. Inhibitory capacities of the antioxidants were investigated both in chemical models containing the precursors (tripalmitoyl glycerol, 1,2-dipalmitoyl-sn-glycerol, monopalmitoyl glycerol, and sodium chloride) of 3-MCPD esters and in oil models (rapeseed oil and sodium chloride). Six antioxidants, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), tert-butyl hydroquinone (TBHQ), propyl gallate (PG), L-ascorbyl palmitate (AP), and α-tocopherol (VE), were found to exhibit inhibiting capacities on 3-MCPD ester formation both in chemical models and in oil models. TBHQ provided the highest inhibitory capacity both in chemical models and in oil models; 44% of 3-MCPD ester formation was inhibited in the presence of TBHQ (66 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min, followed by PG and AP. BHT, BHA, and VE appeared to have weaker inhibitory abilities in both models. VE exhibited the lowest inhibition rate; 22% of 3-MCPD esters were inhibited in the presence of VE (172 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min. In addition, the inhibition rates of PG and VE decreased dramatically with an increase in temperature or heating time. The results suggested that some antioxidants, such as TBHQ, PG, and AP, could be the potential inhibitors of 3-MCPD esters in practice.

Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.

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Song, Jin-Ho; Yeh, Jay Z

2012-05-10

Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7 μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Non-Dioxin-Like Polychlorinated Biphenyls Inhibit G-Protein Coupled Receptor-Mediated Ca2+ Signaling by Blocking Store-Operated Ca2+ Entry.

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Se-Young Choi

Full Text Available Polychlorinated biphenyls (PCBs are ubiquitous pollutants which accumulate in the food chain. Recently, several molecular mechanisms by which non-dioxin-like (NDL PCBs mediate neurodevelopmental and neurobehavioral toxicity have been elucidated. However, although the G-protein coupled receptor (GPCR is a significant target for neurobehavioral disturbance, our understanding of the effects of PCBs on GPCR signaling remains unclear. In this study, we investigated the effects of NDL-PCBs on GPCR-mediated Ca2+ signaling in PC12 cells. We found that ortho-substituted 2,2',6-trichlorinated biphenyl (PCB19 caused a rapid decline in the Ca2+ signaling of bradykinin, a typical Gq- and phospholipase Cβ-coupled GPCR, without any effect on its inositol 1,4,5-trisphosphate production. PCB19 reduced thapsigargin-induced sustained cytosolic Ca2+ levels, suggesting that PCB19 inhibits SOCE. The abilities of other NDL-PCBs to inhibit store-operated Ca2+ entry (SOCE were also examined and found to be of similar potencies to that of PCB19. PCB19 also showed a manner equivalent to that of known SOCE inhibitors. PCB19-mediated SOCE inhibition was confirmed by demonstrating the ability of PCB19 to inhibit the SOCE current and thapsigargin-induced Mn2+ influx. These results imply that one of the molecular mechanism by which NDL-PCBs cause neurobehavioral disturbances involves NDL-PCB-mediated inhibition of SOCE, thereby interfering with GPCR-mediated Ca2+ signaling.

Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

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Liu, Jiwen (Jim); Lee, TaeWeon; DeFronzo, Ralph A.

2012-01-01

Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible. PMID:22923645

Selective inhibition of type 2 fatty acid synthetase by the antibiotic thiolactomycin

International Nuclear Information System (INIS)

Nishida, Ikuo; Kawaguchi, Akihiko; Yamada, Mitsuhiro

1984-01-01

The antibiotic thiolactomycin inhibits the fatty acid synthesis from both [1- 14 C]-acetate and [2 14 C] malonyl-CoA of spinach leaves, developing castor bean endosperms and avocado mesocarp. On the other hand, fatty acid synthetases of Brevibacterium ammoniagenes and Corynebacterium glutamicum are much less sensitive to this antibiotic. As Hayashi et al. have indicated in their paper that thiolactomycin inhibits fatty acid synthetase of Escherichia coli but has little effect on the synthetases of yeast and rat liver, thiolactomycin is suggested to be a selective inhibitor of type 2 fatty acid synthetases. (author)

Selective inhibition of type 2 fatty acid synthetase by the antibiotic thiolactomycin

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Nishida, Ikuo; Kawaguchi, Akihiko; Yamada, Mitsuhiro (Tokyo Univ. (Japan). Faculty of Science)

1984-03-01

The antibiotic thiolactomycin inhibits the fatty acid synthesis from both (1-/sup 14/C)-acetate and (2/sup 14/C) malonyl-CoA of spinach leaves, developing castor bean endosperms and avocado mesocarp. On the other hand, fatty acid synthetases of Brevibacterium ammoniagenes and Corynebacterium glutamicum are much less sensitive to this antibiotic. As Hayashi et al. have indicated in their paper that thiolactomycin inhibits fatty acid synthetase of Escherichia coli but has little effect on the synthetases of yeast and rat liver, thiolactomycin is suggested to be a selective inhibitor of type 2 fatty acid synthetases.

Environmentally persistent free radical-containing particulate matter competitively inhibits metabolism by cytochrome P450 1A2

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Reed, James R., E-mail: rreed@lsuhsc.edu [Department of Pharmacology and Experimental Therapeutics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 533 Bolivar St., New Orleans, LA 70112 (United States); Cruz, Albert Leo N. dela, E-mail: adelac2@tigers.lsu.edu [Department of Environmental Sciences and LSU Superfund Research Center, Louisiana State University A& M College, Baton Rouge, LA 70803 (United States); Lomnicki, Slawo M., E-mail: slomni1@lsu.edu [Department of Environmental Sciences and LSU Superfund Research Center, Louisiana State University A& M College, Baton Rouge, LA 70803 (United States); Backes, Wayne L., E-mail: wbacke@lsuhsc.edu [Department of Pharmacology and Experimental Therapeutics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 533 Bolivar St., New Orleans, LA 70112 (United States)

2015-12-01

Combustion processes generate different types of particulate matter (PM) that can have deleterious effects on the pulmonary and cardiovascular systems. Environmentally persistent free radicals (EPFRs) represent a type of particulate matter that is generated after combustion of environmental wastes in the presence of redox-active metals and aromatic hydrocarbons. Cytochromes P450 (P450/CYP) are membrane-bound enzymes that are essential for the phase I metabolism of most lipophilic xenobiotics. The EPFR formed by chemisorption of 2-monochlorophenol to silica containing 5% copper oxide (MCP230) has been shown to generally inhibit the activities of different forms of P450s without affecting those of cytochrome P450 reductase and heme oxygenase-1. The mechanism of inhibition of rat liver microsomal CYP2D2 and purified rabbit CYP2B4 by MCP230 has been shown previously to be noncompetitive with respect to substrate. In this study, MCP230 was shown to competitively inhibit metabolism of 7-benzyl-4-trifluoromethylcoumarin and 7-ethoxyresorufin by the purified, reconstituted rabbit CYP1A2. MCP230 is at least 5- and 50-fold more potent as an inhibitor of CYP1A2 than silica containing 5% copper oxide and silica, respectively. Thus, even though PM generally inhibit multiple forms of P450, PM interacts differently with the forms of P450 resulting in different mechanisms of inhibition. P450s function as oligomeric complexes within the membrane. We also determined the mechanism by which PM inhibited metabolism by the mixed CYP1A2–CYP2B4 complex and found that the mechanism was purely competitive suggesting that the CYP2B4 is dramatically inhibited when bound to CYP1A2. - Highlights: • Combustion of organic pollutants generates long-lived particulate radicals (EPFRs). • Particulate matter (PM) competitively inhibited CYP1A2 activity. • EPFRs were much more potent CYP1A2 inhibitors than other types of PM. • PM interacts differently with different forms of P450. • PM

[Pseudolaric acid B induces G2/M arrest and inhibits invasion and migration in HepG2 hepatoma cells].

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Li, Shuai; Guo, Lianyi

2018-01-01

Objective To investigate the mechanisms of pseudolaric acid B (PAB) blocks cell cycle and inhibits invasion and migration in human hepatoma HepG2 cells. Methods The proliferation effect of PAB on HepG2 cells was evaluated by MTT assay. The effect of PAB on the cell cycle of HepG2 cells was analyzed by flow cytometry. Immunofluorescence cytochemical staining was applied to observe the effect of PAB on the α-tubulin polymerization and expression in HepG2 cells. Transwell TM chamber invasion assay and wound healing assay were performed to detect the influence of PAB on the migration and invasion ability of HepG2 cells. Western blotting was used to determine the expressions of α-tubulin, E-cadherin and MMP-9 in HepG2 cells after treated with PAB. Results PAB inhibited the proliferation of HepG2 cells in a dose-dependent manner and blocked the cell cycle in G2/M phase. PAB significantly changed the polymerization and decreased the expression of α-tubulin. The capacities of invasion and migration of HepG2 cells treated by PAB were significantly depressed. The protein levels of α-tubulin and MMP-9 decreased while the E-cadherin protein level increased. Conclusion PAB can inhibits the proliferation of HepG2 cells by down-regulating the expression of α-tubulin and influencing its polymerization, arresting HepG2 cells in G2/M phase. Meanwhile, PAB also can inhibit the invasion and migration of HepG2 cells by lowering cytoskeleton α-tubulin and MMP-9, and increasing E-cadherin.

Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways

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Tong, Qingyi [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Qing, Yong, E-mail: qingyongxy@yahoo.co.jp [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Yang [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Hu, Xiaojuan; Jiang, Lei [Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China); Wu, Xiaohua, E-mail: wuxh@scu.edu.cn [Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China)

2014-12-01

Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of dioscin. We showed that dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied by obvious blood vessel decrease within solid tumors. We also found dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF-induced blood vessel formation in vivo. We also identified that dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied by the increase of phosphorylated P38MAPK. The results potently suggest that dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways. - Highlights: • Dioscin inhibits tumor growth in vivo and does not exhibit any toxicity. • Dioscin inhibits angiogenesis within solid tumors. • Dioscin inhibits the proliferation, migration, invasion, and tube formation of HUVECs. • Dioscin inhibits VEGF–induced blood vessel formation in vivo. • Dioscin inhibits VEGFR2 signaling pathway as well as AKT/MAPK pathway.

Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells

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Hongshan Ge

2015-01-01

Full Text Available UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality.

Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.

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Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem

2011-06-01

Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.

Inhibition of [3H]nitrendipine binding by phospholipase A2

International Nuclear Information System (INIS)

Goldman, M.E.; Pisano, J.J.

1985-01-01

Phospholipase A 2 from several sources inhibited [ 3 H]nitrendipine binding to membranes from brain, heart and ileal longitudinal muscle. The enzymes from bee venom and Russell's viper venom were most potent, having IC 50 values of approximately 5 and 14 ng/ml, respectively, in all three membrane preparations. Inhibition of binding by bee venom phospholipase A 2 was time- and dose-dependent. Mastoparan, a known facilitator of phospholipase A 2 enzymatic activity, shifted the bee venom phospholipase A 2 dose-response curve to the left. Pretreatment of brain membranes with bee venom phospholipase A 2 (10 ng/ml) for 15 min caused a 2-fold increase in the K/sub d/ without changing the B/sub max/ compared with untreated membranes. Extension of the preincubation period to 30 min caused no further increase in the K/sub d/ but significantly decreased the B/sub max/ to 71% the value for untreated membranes. [ 3 H]Nitrendipine, preincubated with bee venom phospholipase A 2 , was recovered and found to be fully active, indicating that the phospholipase A 2 did not modify the ligand. It is concluded that phospholipase A 2 acts on the membrane at or near the [ 3 H]nitrendipine binding site and that phospholipids play a key role in the interactions of 1,4 dihydropyridine calcium channel antagonists with the dihydropyridine binding site. 33 references, 3 figures, 1 table

Desempeño térmico de cubiertas vegetadas en ciudades de zonas áridas

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Juan Emiliano Flores Asin; Claudia Fernanda Martinez; Maria Alicia Cantón; Erica Norma Correa

2016-01-01

Las cubiertas vegetadas constituyen una estrategia de enverdecimiento urbano que contribuyen a reducir los efectos del calentamiento global, disminuyendo las temperaturas urbanas y los consumos de energía en espacios interiores derivados del acondicionamiento térmico para alcanzar condiciones de confort en verano. Sin embargo, su implementación en zonas áridas está supeditada a la restricción del recurso hídrico. Este trabajo evalúa el desempeño térmico de cubiertas vegetadas con dos especies...

La enfermedad de Chagas en la zona central de Honduras: conocimientos, creencias y prácticas

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Gustavo Ávila Montes

1998-03-01

Full Text Available En el período de noviembre a diciembre de 1991 y en marzo de 1993 se realizó una encuesta en 17 comunidades rurales de la parte central de Honduras. Las comunidades correspondían a dos zonas en las que la enfermedad de Chagas es endémica. En una de las zonas habían tenido lugar actividades de control de la enfermedad. Fueron entrevistados 849 adultos, uno en cada uno de otros tantos hogares familiares. El objetivo de la encuesta fue investigar y comparar en ambas zonas los conocimientos sobre la enfermedad de Chagas y sus mecanismos de transmisión, las prácticas para evitar la presencia de triatómidos en las viviendas, las creencias acerca de los triatómidos y su control, y las fuentes a partir de las cuales la población obtiene información sobre la enfermedad. Se utilizó un cuestionario de 23 preguntas validado y precodificado. Casi 100% de los entrevistados pudieron reconocer el vector y conocían sus hábitos, pero solo 30,1% sabían que el Triatoma es vector transmisor de la enfermedad y apenas 6% pudieron mencionar su relación con una afección cardíaca crónica. El 47,9% de los entrevistados indicó que la responsabilidad de eliminar los triatómidos de la vivienda es personal, aunque 78% consideraron como medida de control la aplicación institucional de insecticidas. El contacto personal entre el funcionario institucional y los miembros de la comunidad fue la principal fuente de información entre los que mencionaron haber oído de la enfermedad de Chagas (41,0%. Los resultados sugieren que al planificar medidas de control se debe incluir el componente de educación sanitaria. Ha de ponerse énfasis en el papel que desempeñan los triatómidos en la transmisión, así como en la importancia de mejorar la vivienda como medida eficaz y sostenible mediante la participación de la comunidad. Este componente deberá ser desarrollado por canales de comunicación interpersonales para obtener un mayor impacto.

Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Luan, Xin; Gao, Yun-Ge; Guan, Ying-Yun; Xu, Jian-Rong; Lu, Qin [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Zhao, Mei [Department of Pharmacy, Shanghai Institute of Health Sciences and Health School Attached to SJTU-SM, 279 Zhouzhu Road, Shanghai 201318 (China); Liu, Ya-Rong; Liu, Hai-Jun [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Fang, Chao, E-mail: fangchao100@hotmail.com [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China)

2014-11-15

Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC.

Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway

International Nuclear Information System (INIS)

Luan, Xin; Gao, Yun-Ge; Guan, Ying-Yun; Xu, Jian-Rong; Lu, Qin; Zhao, Mei; Liu, Ya-Rong; Liu, Hai-Jun; Fang, Chao; Chen, Hong-Zhuan

2014-01-01

Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC

Crise e mercado de trabalho: repercussões no centro e na periferia da Zona Euro = Crisis and labour market: repercussions on the center and periphery of the Eurozone

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Sabadini, Mauricio de Souza

2013-01-01

Full Text Available O objetivo deste artigo é o de observar as tendências verificadas no mercado de trabalho dos países pertencentes à Zona Euro, dando ênfase às semelhanças e diferenças existentes entre aqueles que compõem, por um lado, a periferia e, de outro, o centro desta zona monetária. A hipótese principal aqui levantada é a de que a crise verificada pós-2008 acentuou as disparidades existentes no mercado de trabalho entre estes países, intensificando a divisão internacional do trabalho. Apesar de geograficamente pertencerem à mesma zona monetária e estarem sob a égide dos princípios dos tratados que regem a sua organização, tais países, que possuem estágios de desenvolvimento capitalistas diferenciados, apresentam elementos e características peculiares quanto aos seus mercados de trabalho. Como era de se esperar, as estruturas capitalistas mais frágeis, representadas pelos países periféricos da Zona Euro, mostraram-se muito mais afetadas pela crise, o que não significa dizer que nos países centrais os efeitos sobre o mercado de trabalho foram pequenos. Pelo contrário, o que se observou em seu interior foi também um processo generalizado de flexibilização e intensificação da precarização do trabalho

Pitch Variability in Patients with Parkinson's Disease: Effects of Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus

Science.gov (United States)

Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan

2013-01-01

Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…

β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

Science.gov (United States)

Yu, Xiaomu; Xu, Maoyi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

2017-08-19

Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

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Maya Shakèd

Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun-Ju, E-mail: biohjk@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Hye-Jin [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Kyung-Ae [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Gwon, Mi-Ri; Jin Seong, Sook [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, Shin-Yoon [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Young-Ran, E-mail: yry@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

2015-06-10

Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstream signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. - Highlights: • LCN2 expression is regulated during osteoclast development. • LCN2 suppresses M-CSF-mediated osteoclast precursor proliferation. • LCN2 inhibits RANKL-induced osteoclast differentiation.

Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway.

Science.gov (United States)

Tang, Ning; Shi, Lei; Yu, Zhenlong; Dong, Peipei; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Huang, Shanshan; Deng, Sa; Liu, Kexin; Ma, Tonghui; Wang, Xiaobo; Wu, Lijun; Ma, Xiao-Chi

2016-01-19

Gamabufotalin (CS-6), a main active compound isolated from Chinese medicine Chansu, has been shown to strongly inhibit cancer cell growth and inflammatory response. However, its effects on angiogenesis have not been known yet. Here, we sought to determine the biological effects of CS-6 on signaling mechanisms during angiogenesis. Our present results fully demonstrate that CS-6 could significantly inhibit VEGF triggered HUVECs proliferation, migration, invasion and tubulogenesis in vitro and blocked vascularization in Matrigel plugs impregnated in C57/BL6 mice as well as reduced vessel density in human lung tumor xenograft implanted in nude mice. Computer simulations revealed that CS-6 interacted with the ATP-binding sites of VEGFR-2 using molecular docking. Furthermore, western blot analysis indicated that CS-6 inhibited VEGF-induced phosphorylation of VEGFR-2 kinase and suppressed the activity of VEGFR-2-mediated signaling cascades. Therefore, our studies demonstrated that CS-6 inhibited angiogenesis by inhibiting the activation of VEGFR-2 signaling pathways and CS-6 could be a potential candidate in angiogenesis-related disease therapy.

Corrosion Inhibition and Adsorption Characteristics of Tarivid on Mild Steel in H2SO4

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N. O. Eddy

2010-01-01

Full Text Available The corrosion inhibition and adsorption characteristics of (+/--9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (Tarivid on the corrosion of mild steel has been studied using thermometric and gasometric methods. The study reveals that tarivid inhibits the corrosion of mild steel in H2SO4. The values of inhibition efficiency of tarivid were found to increase as its concentration increased but decreased with increase in temperature. Activation energies of the inhibited corrosion of mild steel ranged from 39.05 to 50.61 kJ/mol. Values of enthalpy change and free energy of adsorption were negative which indicated exothermic and spontaneous adsorption process. Physical adsorption mechanism is proposed from the obtained kinetic and thermodynamic parameters. Langmuir adsorption isotherm model is obeyed from the fit of the experimental data.

Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca2+ Sensor Protein

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Keming Zhou

2017-05-01

Full Text Available Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca2+ binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance.

Polymeric black tea polyphenols inhibit 1,2-dimethylhydrazine induced colorectal carcinogenesis by inhibiting cell proliferation via Wnt/β-catenin pathway

International Nuclear Information System (INIS)

Patel, Rachana; Ingle, Arvind; Maru, Girish B.

2008-01-01

Tea polyphenols like epigallocatechin gallate and theaflavins are established chemopreventive agents for colorectal carcinogenesis. However, studies on evaluating similar chemopreventive properties of thearubigins or polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited. Hence, in the present study we aim to investigate chemopreventive effects along with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Sprague-Dawley rats as experimental model. The present study suggests that PBPs, like other tea polyphenols, also inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and multiplicity. This study also shows that although the pretreatment with PBP extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did not show any additional chemopreventive effects when compared to treatments with PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit colorectal carcinogenesis by decreasing DMH-induced cell proliferation via Wnt/β-catenin pathway. Treatments with PBP extract showed decreased levels of COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by regulating β-catenin by maintaining expression of APC and decreasing inactivation of GSK3β. DMH-induced activation of MAP kinases such as ERK and JNK was also found to be inhibited by treatments with PBP extract. In conclusion, the protective effects of PBP extract could be attributed to inhibition of DMH-induced cellular proliferation probably through β-catenin regulation

Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling.

Science.gov (United States)

Xiong, Hua; Chen, Zhao-Fei; Liang, Qin-Chuan; Du, Wan; Chen, Hui-Min; Su, Wen-Yu; Chen, Guo-Qiang; Han, Ze-Guang; Fang, Jing-Yuan

2009-09-01

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or SOCS3 in colorectal cancer (CRC) cells. SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the proteasome pathway. Up-regulation of SHP1 expression was achieved using a DNA MTI, 5-aza-2'-deoxycytidine (5-aza-dc), which also generated significant down-regulation of JAK2/STAT3/STAT5 signalling. We demonstrate that 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signalling including Bcl-2, p16(ink4a), p21(waf1/cip1) and p27(kip1). Although 5-aza-dc did not significantly inhibit cell invasion, 5-aza-dc did down-regulate expression of focal adhesion kinase and vascular endothelial growth factor in CRC cells. Our results demonstrate that 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling. This study represents the first evidence towards establishing a mechanistic link between inhibition of JAK2/STAT3/STAT5 signalling and the anticancer action of 5-aza-dc in CRC cells that may lead to the use of MTIs as a therapeutic intervention for human colorectal cancer.

Selección y Espaciamiento de Apartarrayos en Líneas de Distribución de 23 kV de la Zona Centro

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L. Cisneros-Villalobos

2015-01-01

Full Text Available En este artículo se analiza una red de distribución urbana de 23 kV típica de la zona central de México. El objetivo es determinar la distancia máxima de separación entre apartarrayos de línea que permita reducir las salidas de los circuitos de distribución por descargas atmosféricas directas e indirectas. Con base en las características eléctricas, ambientales, ceráunicas y geográficas de la zona, niveles de cortocircuito y las sobretensiones provocadas por maniobras rutinarias, se selecciona el apartarrayos siempre con el principal objetivo de determinar su espaciamiento adecuado sobre la línea para que éste funcione apropiadamente. La investigación se lleva a cabo con la ayuda del software llamado Alternative Transients Program (ATP donde se realiza el cálculo de los parámetros de la línea utilizando el modelo de K.C. Lee, las sobretensiones transitorias por onda viajera y por conexión de capacitores también son simuladas. La motivación de este trabajo consiste principalmente en contar con un mayor sustento teórico y técnico (actualmente escueto para determinar el espaciamiento entre apartarrayos de la red de distribución considerada y así aumentar la calidad del suministro eléctrico de la zona.

Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy

NARCIS (Netherlands)

Sarma, Satyam; Li, Na; van Oort, Ralph J.; Reynolds, Corey; Skapura, Darlene G.; Wehrens, Xander H. T.

2010-01-01

Aberrant intracellular Ca(2+) regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR

Estructura forestal de una zona de manglar en la laguna de Coyuca de Benítez, Guerrero

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Benjamín Castillo Elías

2018-01-01

Full Text Available Los manglares son un recurso forestal de gran importancia en los humedales, tanto por su diversidad y estructura maderable como por los beneficios ambientales y socioeconómicos que representan. Su composición depende de factores ambientales, condiciones edáficas, acción antrópica y de la capacidad de interrelacionarse entre sí para compartir un espacio. En el estado de Guerrero existen solo registros que indican áreas de distribución de bosques de manglar y descripción de especies. El objetivo fue conocer la importancia ecológica del manglar adjunto a las comunidades de El Carrizal y Playa Azul, municipio Coyuca de Benítez, Guerreo, a través de la obtención de su densidad y abundancia relativa, diversidad y volumen maderable. De julio a diciembre del 2016, se obtuvo la composición estructural de la vegetación asociada al manglar, con base en 10 unidades de 10 ×10 m (100 m2 y una intensidad de muestreo de 4 %. Se identificaron nueve especies forestales asociadas al ecosistema de manglar. Se determinó un volumen total de 10.30 m3 rollo total árbol, de los cuales Laguncularia racemosa (mangle blanco aporta el mayor volumen con 8.05 m3 rollo total árbol; mientras que para el área total de la zona de humedal el valor fue de 218.92 m3 rollo total árbol. Con esta investigación se logró conocer la composición estructural de las especies de flora en el área de estudio, y la importancia ecológica del manglar constituido por L. racemosa, representada como alternativa de conservación para la zona.

Antihelminthic drug niclosamide inhibits CIP2A and reactivates tumor suppressor protein phosphatase 2A in non-small cell lung cancer cells.

Science.gov (United States)

Kim, Myeong-Ok; Choe, Min Ho; Yoon, Yi Na; Ahn, Jiyeon; Yoo, Minjin; Jung, Kwan-Young; An, Sungkwan; Hwang, Sang-Gu; Oh, Jeong Su; Kim, Jae-Sung

2017-11-15

Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged asan anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells. We performed a drug-repurposing screen and identified niclosamide asa CIP2A suppressor in NSCLC cells. Niclosamide inhibited cell proliferation, colony formation, and tumor sphere formation, and induced mitochondrial dysfunction through increased mitochondrial ROS production in NSCLC cells; however, these effects were rescued by CIP2A overexpression, which indicated that the antitumor activity of niclosamide was dependent on CIP2A. We found that niclosamide increased PP2A activity through CIP2A inhibition, which reduced the phosphorylation of several oncogenic proteins. Moreover, we found that a niclosamide analog inhibited CIP2A expression and increased PP2A activity in several types of NSCLC cells. Finally, we showed that other well-known PP2A activators, including forskolin and FTY720, did not inhibit CIP2A and that their activities were not dependent on CIP2A. Collectively, our data suggested that niclosamide effectively suppressed CIP2A expression and subsequently activated PP2A in NSCLC cells. This provided strong evidence for the potential use of niclosamide asa PP2A-activating drug in the clinical treatment of NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

Estrategias para establecer pastos de temporal en zonas semiáridas de México.

OpenAIRE

Hernández Guzmán, Filogonio Jesús

2013-01-01

Para incrementar la probabilidad de establecimiento de pastos, en siembras de temporal en zonas semiáridas, se caracterizaron física y fisiológicamente semillas de Banderita, Navajita; Buffel y Rhodes y, en base a dimensiones y utilizando tamiz, se clasificaron por tamaño de cariópside (TC) en chicos (Cch), medianos (CM) y grandes (CG). En Banderita y Buffel, los diámetros de tamiz para CG, CM y Cch fueron de 0.70, 0.59 y 0.50 mm y para Navajita y Rhodes, 0.59, 0.50 y 0.42 mm, respectivamente...

Características clínicas da doença diarréica em lactentes na Zona da Mata Meridional do estado de Pernambuco Clinical characteristics of diarrheal disease in suckling children in the Zona da Mata Meridional in the State of Pernambuco

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Giselia Alves Pontes da Silva

2002-12-01

Full Text Available OBJETIVOS: descrever as características clínicas dos episódios diarréicos apresentados por um grupo de crianças residentes na Zona da Mata Meridional do estado de Pernambuco nos primeiros seis meses de vida. MÉTODOS: o desenho do estudo é uma série de casos dele fazem parte todas as crianças acompanhadas dentro de um estudo de coorte realizado em quatro cidades da Zona da Mata Meridional do estado de Pernambuco e que durante o período de observação apresentaram pelo menos um episódio de doença diarréica. RESULTADOS: foram acompanhados 264 episódios de doença diarréica, que ocorreram em 239 crianças. A duração dos episódios variou entre um e 31 dias, sendo a mediana de dois dias e a moda de um dia. Um total de 93,5% dos episódios se auto-limitou em até sete dias. A maioria das crianças apresentou um episódio de diarréia durante o período de observação. Houve necessidade de hospitalização em 18 episódios (6,8%. Não foi observado nenhum óbito. CONCLUSÕES: a evolução clínica da doença diarréica quando estudada na comunidade é benigna, com episódios diarréicos de curta duração e levando a baixos índices de hospitalização.OBJECTIVES: to describe clinical characteristics of diarrhea episodes in a group of children residing in the Zona da Mata Meridional in the State of Pernambuco during the first six months of life. METHODS: the study's design is a case series comprising all children followed-up within a cohort study accomplished in four cities of the Zona da Mata Meridional of the State of Pernambuco who during observation had at least one episode of diarrheal disease. RESULTS: 264 episodes of diarrhea were followed-up in 239 children. The episodes lasted between one and 31 days, with the median of two days and the mode of one day. 93,5% of the episodes were self-limited to seven days. The majority of the children had one diarrhea episode during observation. Hospitalization was required in 18 episodes

Development of norepinephrine transporter reuptake inhibition assays using SK-N-BE(2C cells

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Ann M. Decker

2018-05-01

Full Text Available This report describes efforts to develop and validate novel norepinephrine transporter reuptake inhibition assays using human neuroblastoma SK-N-BE(2C cells in 24-well format. Before conducting the assays, the SK-N-BE(2C cells were first evaluated for their ability to uptake [3H]norepinephrine and were shown to have a saturable uptake with a KM value of 416 nM. Using this determined KM value, reuptake inhibition assays were then conducted with a variety of ligands including antidepressants, as well as piperazine and phenyltropane derivatives. The results obtained with the SK-N-BE(2C cells indicate that this model system can detect a range of ligand potencies, which compare well with other established transporter assays. Our data suggest that SK-N-BE(2C cells have potential utility to serve as another model system to detect norepinephrine reuptake inhibition activity.

Inhibition of the entomopathogenic fungus Metarhizium anisopliae in vitro by the bed bug defensive secretions (E)-2-hexenal and (E)-2-octenal

Science.gov (United States)

The two major aldehydes (E)-2-hexenal and (E)-2-octenal emitted as defensive secretions by bed bugs Cimex lectularius L. (Hemiptera: Cimicidae), inhibit the in vitro growth of Metarhizium anisopliae (Metsch.) Sokorin (Hypocreales: Clavicipitaceae). These chemicals inhibit fungal growth by direct con...

Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib.

Science.gov (United States)

Kirane, Amanda; Toombs, Jason E; Larsen, Jill E; Ostapoff, Katherine T; Meshaw, Kathryn R; Zaknoen, Sara; Brekken, Rolf A; Burrows, Francis J

2012-09-01

Although cyclooxygenase-2 (COX-2) inhibitors, such as the late stage development drug apricoxib, exhibit antitumor activity, their mechanisms of action have not been fully defined. In this study, we characterized the mechanisms of action of apricoxib in HT29 colorectal carcinoma. Apricoxib was weakly cytotoxic toward naive HT29 cells in vitro but inhibited tumor growth markedly in vivo. Pharmacokinetic analyses revealed that in vivo drug levels peaked at 2-4 µM and remained sufficient to completely inhibit prostaglandin E(2) production, but failed to reach concentrations cytotoxic for HT29 cells in monolayer culture. Despite this, apricoxib significantly inhibited tumor cell proliferation and induced apoptosis without affecting blood vessel density, although it did promote vascular normalization. Strikingly, apricoxib treatment induced a dose-dependent reversal of epithelial-mesenchymal transition (EMT), as shown by robust upregulation of E-cadherin and the virtual disappearance of vimentin and ZEB1 protein expression. In vitro, either anchorage-independent growth conditions or forced EMT sensitized HT29 and non-small cell lung cancer cells to apricoxib by 50-fold, suggesting that the occurrence of EMT may actually increase the dependence of colon and lung carcinoma cells on COX-2. Taken together, these data suggest that acquisition of mesenchymal characteristics sensitizes carcinoma cells to apricoxib resulting in significant single-agent antitumor activity.

Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

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Zhao Han

Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

Effects of exposure of epididymal boar spermatozoa to seminal plasma on the binding of zona pellucida proteins during in vitro capacitation

NARCIS (Netherlands)

Harkema, W.; Colenbrander, B.; Engel, B.; Woelders, H.

2004-01-01

The purpose of the investigation was to determine whether seminal plasma plays a role in the increase during in vitro capacitation of the number of boar spermatozoa with enhanced binding of zona pellucida proteins. Ejaculated spermatozoa and spermatozoa collected from the caudae epididymides of

Nuevas aportaciones a la gestión informatizada de derrames de hidrocarburos: su aplicación a “zonas refugio”

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José Ramón Bergueiro

2011-06-01

Full Text Available The purpose of this paper is to describe most of the procedures to follow in deciding whether you should transfer a tanker wrecked in a "refuge zone". In reaching this decision, it should consider different procedures, in order to objectify the best decision. It is important to know very well the features and infrastructures of the different coastal areas, which can be considered as possible "refuge zones". Based on the foregoing analysis, it has developed a program consisting of several modules to permit compute data of great importance, among which include matrices of environmental and infrastructural values that allow for the calculation of certain factors for transfer actions and preparation of the tanker (transfer time of the tanker, berthing time and connection time to the pumping systems, time of emptying the oil in storage tanks, transfer to another tanker, etc. In addition, this program allows us to estimate the costs of cleaning and restoration, as well as losses in the tourism sector. Keywords: Hydrocarbons; Place of refuge; Oil spills El objeto del presente trabajo es el de describir la mayor parte de los procedimientos a seguir para decidir si es aconsejable trasladar un petrolero siniestrado a una “zona refugio”. Para tomar esta decisión se deberán considerar diferentes procedimientos, con la finalidad de objetivizar al máximo dicha decisión. Es de gran importancia conocer muy bien las características y las infraestructuras de las diferentes zonas costeras que pueden ser consideradas posibles “zonas refugio”. En base a todo lo anterior, se ha desarrollado un programa formado por varios módulos que permiten obtener datos de gran importancia, entre los que se incluyen las matrices de valores ambientales e infraestructurales, y que permite el cálculo de determinados factores determinantes para las actuaciones de traslado y preparación del petrolero (tiempo de traslado del petrolero, tiempo de atraque y conexión a los

Immune response in rabbit ovaries following infection of a recombinant myxoma virus expressing rabbit zona pellucida protein B

International Nuclear Information System (INIS)

Gu Wenyi; Holland, Michael; Janssens, Peter; Seamark, Robert; Kerr, Peter

2004-01-01

In this study, we investigated the autoimmune response in rabbit ovaries following infection with a recombinant myxoma virus expressing rabbit zona pellucida protein B (MV-ZPB). A specific IgG antibody response to ZPB was elicited in the serum of infected rabbits and the antibody strongly bound to the zona pellucida of oocytes in secondary and tertiary follicles. T cell infiltration in the ovary was detected in a small proportion of the infected rabbits. In spite of this, the mean number of preovulatory and tertiary follicles in the ovary was significantly reduced at 30 days postinfection compared with that of the infected and uninfected controls. Histological analysis revealed that the cortex and medulla of these ovaries had accumulated a large number of probably luteinized cells and there were no follicles in these areas, indicating the ovaries were in a severe pathological condition. The data suggest that the delivery of ZP antigens using a recombinant myxoma virus is a prospective way to develop immunocontraceptive vaccines for rabbit population control, but that more understanding of the kinetics of the autoimmune response induced by viral delivery is needed

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway

International Nuclear Information System (INIS)

Lee, Cheol-Jung; Lee, Mee-Hyun; Yoo, Sun-Mi; Choi, Kyung-Il; Song, Ji-Hong; Jang, Jeong-Hoon; Oh, Sei-Ryang; Ryu, Hyung-Won; Lee, Hye-Suk; Surh, Young-Joon; Cho, Yong-Yeon

2015-01-01

Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved. Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2 +/+ and RSK2 −/− MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence. Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and −9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs. These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. The online version of this article (doi:10.1186/s12885-015-1580-7) contains

Targeting of the BLT2 in chronic myeloid leukemia inhibits leukemia stem/progenitor cell function

Energy Technology Data Exchange (ETDEWEB)

Xiao, Meifang; Ai, Hongmei; Li, Tao [Department of Laboratory Medicine, JingZhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Rajoria, Pasupati; Shahu, Prakash [Department of Clinical Medicine, Medical School of Yangtze University, Jingzhou (China); Li, Xiansong, E-mail: lixiansongjz@hotmail.com [Department of Neurosurgery, JingZhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China)

2016-04-15

Imatinib, a tyrosine kinase inhibitor (TKI) has significantly improved clinical outcome for chronic myeloid leukemia (CML) patients. However, patients develop resistance when the disease progresses to the blast phase (BP) and the mechanisms are not well understood. Here we show that BCR-ABL activates BLT2 in hematopoietic stem/progenitor cells to promote leukemogenesis and this involves the p53 signaling pathway. Compared to normal bone marrow (NBM), the mRNA and protein levels of BLT2 are significantly increased in BP-CML CD34{sup +} stem/progenitor cells. This is correlated with increasing BCR-ABL expression. In contrast, knockdown of BCR-ABL or inhibition of its tyrosine kinase activity decreases Blt2 protein level. BLT2 inhibition induces apoptosis, inhibits proliferation, colony formation and self-renewal capacity of CD34{sup +} cells from TKI-resistant BP-CML patients. Importantly, the inhibitory effects of BCR-ABL TKI on CML stem/progenitor cells are further enhanced upon combination with BLT2 inhibition. We further show that BLT2 activation selectively suppresses p53 but not Wnt or BMP-mediated luciferase activity and transcription. Our results demonstrate that BLT2 is a novel pathway activated by BCR-ABL and critically involved in the resistance of BP-CML CD34{sup +} stem/progenitors to TKIs treatment. Our findings suggest that BLT2 and p53 can serve as therapeutic targets for CML treatment. - Highlights: • BCR-ABL regulates BLT2 expression to promote leukemogenesis. • BLT2 is essential to maintain CML cell function. • Activation of BLT2 suppresses p53 signaling pathway in CML cells. • Inhibition of BLT2 and BCR-ABL synergize in eliminating CML CD34{sup +} stem/progenitors.

The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

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Ramón A. Lorca

2011-01-01

Full Text Available Although the physiological function of the cellular prion protein (PrPC remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+.

Spatial distribution of metals in soil samples from Zona da Mata, Pernambuco, Brazil using XRF technique

International Nuclear Information System (INIS)

Fernandez, Zahily Herrero; Santos Junior, Jose Araujo dos; Amaral, Romilton dos Santos; Menezes, Romulo Simoes Cezar; Santos, Josineide Marques do Nascimento; Bezerra, Jairo Dias; Damascena, Kennedy Francys Rodrigues; Silva, Edvane Borges da; Silva, Alberto Antonio da

2015-01-01

Soil contamination is today one of the most important environmental issues for society. In the past, soil pollution was not considered as important as air and water contamination, because this was more difficult to be controlled, becoming an important topic in studies of environmental protection worldwide. Based on this, this paper provides information on the determination of metals in soil samples collected in Zona da Mata, Pernambuco, Brazil, where normally the application of pesticides, insecticides and other agricultural additives are used in a disorderly manner and without control. A total of 24 sampling points were monitored. The analysis of Mn, Fe, Ni, Zn, Br, Rb, Sr, Pb, Ti, La, Al, Si and P were performed using Energy Dispersive X-Ray Fluorescence. In order to assess the development of analytical method, inorganic Certified Reference Materials (IAEA-SOIL-7 and SRM 2709) were analyzed. In each sampling site, the geoaccumulation index were calculated to estimate the level of metal contamination in the soil, this was made taking into account the resolution 460 of the National Environmental Council (CONAMA in Portuguese). The elemental distribution patterns obtained for each metal were associated with different pollution sources. This assessment provides an initial description of pollution levels presented by metals in soils from several areas of Zona da Mata, providing quantitative evidence and demonstrating the need to improve the regulation of agricultural and industrial activities. (author)

Spatial distribution of metals in soil samples from Zona da Mata, Pernambuco, Brazil using XRF technique

Energy Technology Data Exchange (ETDEWEB)

Fernandez, Zahily Herrero; Santos Junior, Jose Araujo dos; Amaral, Romilton dos Santos; Menezes, Romulo Simoes Cezar; Santos, Josineide Marques do Nascimento; Bezerra, Jairo Dias; Damascena, Kennedy Francys Rodrigues, E-mail: zahily1985@gmail.com, E-mail: jaraujo@ufpe.br, E-mail: romilton@ufpe.br, E-mail: rmenezes@ufpe.br, E-mail: neideden@hotmail.com, E-mail: jairo.dias@ufpe.br, E-mail: kennedy.eng.ambiental@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Centro de Tecnologia e Geociencias. Departamento de Energia Nuclear; Alvarez, Juan Reinaldo Estevez, E-mail: jestevez@ceaden.cu [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear (CEADEN), Havana (Cuba); Silva, Edvane Borges da, E-mail: edvane.borges@pq.cnpq.br [Universidade Federal de Pernambuco (UFPE), Vitoria de Santo Antao, PE (Brazil). Nucleo de Biologia; Franca, Elvis Joacir de; Farias, Emerson Emiliano Gualberto de, E-mail: ejfranca@cnen.gov.br, E-mail: emersonemiliano@yahoo.com.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Silva, Alberto Antonio da, E-mail: alberto.silva@barreiros.ifpe.edu.br [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Barreiros, PE (Brazil)

2015-07-01

Soil contamination is today one of the most important environmental issues for society. In the past, soil pollution was not considered as important as air and water contamination, because this was more difficult to be controlled, becoming an important topic in studies of environmental protection worldwide. Based on this, this paper provides information on the determination of metals in soil samples collected in Zona da Mata, Pernambuco, Brazil, where normally the application of pesticides, insecticides and other agricultural additives are used in a disorderly manner and without control. A total of 24 sampling points were monitored. The analysis of Mn, Fe, Ni, Zn, Br, Rb, Sr, Pb, Ti, La, Al, Si and P were performed using Energy Dispersive X-Ray Fluorescence. In order to assess the development of analytical method, inorganic Certified Reference Materials (IAEA-SOIL-7 and SRM 2709) were analyzed. In each sampling site, the geoaccumulation index were calculated to estimate the level of metal contamination in the soil, this was made taking into account the resolution 460 of the National Environmental Council (CONAMA in Portuguese). The elemental distribution patterns obtained for each metal were associated with different pollution sources. This assessment provides an initial description of pollution levels presented by metals in soils from several areas of Zona da Mata, providing quantitative evidence and demonstrating the need to improve the regulation of agricultural and industrial activities. (author)

Effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

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Lubin Xu

2017-06-01

Full Text Available Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR and/or urine albumin/creatinine ratio (ACR changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD, −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23] or in patients with chronic kidney disease (CKD (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]. SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54], and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]. Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06], but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]. Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

Vulnerabilidades sociais e juvenil nos mananciais da zona sul da cidade de São Paulo

OpenAIRE

Borelli,Elizabeth

2012-01-01

http://dx.doi.org/10.1590/S1414-49802012000100006 Este artigo é um produto parcial da pesquisa “Reflexos da Vulnerabilidade Socioambiental nas Manifestações Musicais dos Jovens Paulistanos da Periferia”, identificando como recorte geográfico a periferia da Zona Sul da cidade de São Paulo. Trata-se de uma região que começou a se formar devido à ocupação populacional desordenada em áreas de manancial, onde a vulnerabilidade social é agravada por situações de risco e degradação ambiental, da...

Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

Science.gov (United States)

Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

2015-04-15

Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.

Science.gov (United States)

Deng, Zhao; Luo, Pei; Lai, Wen; Song, Tongxing; Peng, Jian; Wei, Hong-Kui

2017-12-09

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 μg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy. Copyright © 2017. Published by Elsevier Inc.

Curcumin inhibits activation of TRPM2 channels in rat hepatocytes

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E. Kheradpezhouh

2016-04-01

Full Text Available Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca2+ homeostasis, resulting in a sustained elevation of the free cytosolic Ca2+ concentration ([Ca2+]c in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca2+ entry through Transient Receptor Potential Melastatin 2 (TRPM2 channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E-1,7-bis(4-hydroxy-3-methoxyphenyl-1,6-heptadiene-3,5-dione, a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5 µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca2+]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50 nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels.

Growth inhibition and radiosensitization of Celecoxib in nasopharyngeal caricnoma cell line CNE-2

International Nuclear Information System (INIS)

Xu Xinhua; Yi Fang; Fu Xiangyang; Zhang Xiaohong; Wang Yanlin; Zhang Changju; Du Jingtao

2009-01-01

Objective: To investigate the growth inhibition and radiosensitization of Celecoxib in human nasopharyngeal carcinoma cell line CNE-2. Methods: CNE-2 growth inhibition by Celecoxib was evaluated by MTT method. Apoptosis-related changes in morphology were observed by transmission electron microscopy(TEM). Cell cycle distribution and apoptosis rate were measured by flowcytometry(FCM). The expression of COX-2 protein was observed by SP method after the treatment of Celecoxib. Cells were randomly planted into four groups: irradiation control (Ci), drug group (Cd), irradiation group (R), and Celecoxib plus irradiation group (D + R). Single irradiation of 2,4,6,8, and 10 Gy were administered for colonogenic assay. Cell cycle distribution and apoptosis rate were analyzed at 6 Gy irradiation. Results: The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner, the IC 50 was 80 μmol/L. After the treatment, cell ratio of G 0 and G 1 phases wasinereased (47.03 ± 2.76 vs 56.17 ± 1.95, t=4.68, P=0.010), whereas the ratio of S and G 2 /M phases was decreased (33.07 ± 1.86 vs 24.87 ± 1.76, t=5.54,P =0.010;19.30 ± 0.53:17.73 ± 0.83, t=2.75, P=0.050), and the apoptosis rate was increased (1.57 ± 0.47:10.47 ± 0.31,t=27.39, P=0.000) in a dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by TEM. SP method showed that Celeib decreased COX-2 expression (17.48 ± 0.34 vs 12.82 ± 0.51, t=13.20, P=0.00). The sensitivity ratio (D 0 ) was 1.15. FCM showed that the percentage of cells in G 2 /M phase was significanty more in R and D + R groups than in Ci and Cd groups (68.00 ± 1.65, 54.27 ± 5.74,17.60 ± 0.80,14.86 ± 1.23, t=47.70,P=0.000; t=11.63, P=0.000), and also significantly different between R group and D + R group (t=3.99, P= 0.020). The apoptosis rate was higher in R and D + R groups than Ci and Cd groups(4.83 ± 0.97,9.50 ± 1.35,1.33 ± 0.86 and 2.28 ± 0.42, t=4.67, P=0.010; t

Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway

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Jinhui Wu

2017-05-01

Full Text Available Chondrosarcomas (CS is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F. called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots. After treatment of celastrol, the proliferation, migration and invasion were significantly inhibited; whereas the apoptosis was largely induced in human CS cell lines. In addition, celastrol inhibited the expression of CIP2A, c-MYC, and suppressed apoptotic proteins BAX and caspase-8 in human CS cells, on the other hand, it induced the expression of antiapoptotic protein Bcl-2. Finally, knockdown of CIP2A also inhibited the migration and invasion and induced apoptosis of human CS cells. To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS.

1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial–mesenchymal transition in colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan, E-mail: wangpengyuan2014@126.com

2015-12-04

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial–mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. - Highlights: • TGF-β1/β2-induced model of EMT was used in this study to test the effect of 1,25(OH)2D3 on EMT in colon cancer cells. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased migration and invasion. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased level of EMT-related transcription factors. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased expression of F-actin in SW-480 cells.

Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

International Nuclear Information System (INIS)

Fitzgerald, Kent; Bergeron, Marcelle; Willits, Christopher; Bowers, Simeon; Aubele, Danielle L.; Goldbach, Erich; Tonn, George; Ness, Daniel; Olaharski, Andrew

2013-01-01

Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646 decreased

Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

Energy Technology Data Exchange (ETDEWEB)

Fitzgerald, Kent, E-mail: Kent.fitzgerald@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bergeron, Marcelle, E-mail: Marcelle.bergeron@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Willits, Christopher, E-mail: Chris.willits@elan.com [Pharmacological Sciences, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Bowers, Simeon, E-mail: Simeon.bowers@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Aubele, Danielle L., E-mail: Danielle.aubele@elan.com [Chemistry, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Goldbach, Erich, E-mail: Erich.goldbach@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Tonn, George, E-mail: George.tonn@elan.com [Drug Metabolism and Pharmacokinetics, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Ness, Daniel, E-mail: Dan.ness@elan.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States); Olaharski, Andrew, E-mail: andrew.olaharski@agios.com [Nonclinical Safety Evaluation, Elan Pharmaceuticals Inc., 180 Oyster Point Boulevard, South San Francisco, CA 94080 (United States)

2013-05-15

Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646

P2-2: Effects of Color Preview History on Inter-Trial Inhibition of Selective Attention

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Eunsam Shin

2012-10-01

Full Text Available The distractor previewing effect (DPE refers to the phenomenon that search times for target colors that were previewed (target preview or TP in a preceding target-absent display (TAD are slower than for distractor colors that were previewed (distractor preview, DP in the TAD. The DPE is explained as attentional inhibition for the features associated with TADs. We investigated history effects of this inter-trial inhibition by manipulating color preview history and examined the DPE using RT and the N2pc (an electrophysiological index of attention allocation. The TAD, ranging from 0 to 2, was followed by a target-present display in which participants responded to the shape of a color-oddball. For the 2TADs, a single color (red or green was repeated twice or the two colors were alternated, resulting in TTP, DDP, TDP, and DTP conditions depending on which color (target or distractor in the search display was previewed. The 1TADs resulted in the TP and the DP, and the 0TADs comprised immediate search trials. RTs showed: (a the TP was slower than the DP; (b the TTP and DDP were slowest and fastest, respectively, and between these the DTP was slower than the TDP; (c the TTP-DDP difference doubled the TP-DP difference due to the RT increase in the TTP. The conditions with slower RTs corresponded with late onsets and smaller amplitudes in the N2pc. These results suggest that effects of color preview history are cumulative with weight on more recent events and support the idea of inter-trial inhibition of target selection.

NHERF1 regulates actin cytoskeleton organization through modulation of α-actinin-4 stability.

Science.gov (United States)

Sun, Licui; Zheng, Junfang; Wang, Qiqi; Song, Ran; Liu, Hua; Meng, Ran; Tao, Tao; Si, Yang; Jiang, Wenguo; He, Junqi

2016-02-01

The actin cytoskeleton is composed of a highly dynamic network of filamentous proteins, yet the molecular mechanism that regulates its organization and remodeling remains elusive. In this study, Na(+)/H(+) exchanger regulatory factor (NHERF)-1 loss-of-function and gain-of-function experiments reveal that polymerized actin cytoskeleton (F-actin) in HeLa cells is disorganized by NHERF1, whereas actin protein expression levels exhibit no detectable change. To elucidate the molecular mechanism underlying actin cytoskeleton disorganization by NHERF1, a combined 2-dimensional electrophoresis-matrix-assisted laser desorption/ionization-time of flight mass spectrometry approach was used to screen for proteins regulated by NHERF1 in HeLa cells. α-Actinin-4, an actin cross-linking protein, was identified. Glutathione S-transferase pull-down and coimmunoprecipitation studies showed the α-actinin-4 carboxyl-terminal region specifically interacted with the NHERF1 postsynaptic density 95/disc-large/zona occludens-1 domain. The NHERF1/α-actinin-4 interaction increased α-actinin-4 ubiquitination and decreased its expression levels, resulting in actin cytoskeleton disassembly. Our study identified α-actinin-4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1. © FASEB.

Abordagem do paciente ferido por arma branca na zona de Ziedler

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Decio Luis Portella

2016-10-01

Full Text Available Introdução: Ferimentos cardíacos penetrantes já foram considerados letais e intratáveis. Homero fez a primeira descrição da morte de Sarpedon em A Ilíada, em 3000 a.C. Em 1883, Billroth afirmou em um Congresso Europeu de Cirurgia que "o cirurgião que tentar suturar um ferimento cardíaco deverá perder o respeito de seus colegas". Em 1897, Rehn apresentou o primeiro caso bem sucedido de cardiorrafia de ventrículo direito Cerca de 87% das lesões cardiovasculares são, em particular, oriundas de trauma penetrante. E, as lesões ventriculares são mais frequentes que as atriais Objetivo: Descrever a abordagem realizada no serviço para pacientes com ferimento por arma branca (FAB na zona de Ziedler, através da experiência de sete casos relatados em 7 anos Discutir a relevância da utilização do FAST (Focused Assesment with Sonography for Trauma na avaliação primária do protocolo ATLS (Advanced Trauma Life Support e a sequência de reavaliação, e analisar qual o melhor procedimento diagnóstico e terapêutico para cada apresentação clínica do paciente. Método: Realizou-se um estudo retrospectivo, descritivo e analítico de sete pacientes atendidos no pronto atendimento do Politrauma do Conjunto Hospitalar de Sorocaba. O conteúdo deste trabalho foi obtido através da revisão de prontuário e descrição cirúrgica, registro fotográficos, além de revisão da literatura. Resultados: A experiência do serviço mostra que a abordagem inicial descrita pelo ATLS é fundamental para guiar o atendimento ao ferido. Quando da realização do FAST na avaliação primária indicando ausência de líquido na janela pericárdica deve-se manter o paciente com FAB em zona de Ziedler na sala de urgência sendo assistido por profissionais capacitados. A necessidade de Tomografia Computadorizada com contraste demonstra-se relevante para os casos em que há FAST inconclusivo, ainda que com paciente estável. A amostra exibe um caso de

Maestros en zonas de conflicto

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Mauricio Lizarralde

2003-10-01

Full Text Available Partiendo de los relatos de los mismos maestros, se establecen las características de los procesos de socialización y construcción de identidad en el contexto de la guerra, ubicando luego las formas de enunciación de esa identidad por parte de los propios maestros. El que sus interacciones cotidianas se desarrollen en un contexto caracterizado por el miedo generado por las vivencias de acciones de guerra como combates, masacres, señalamientos y amenazas, además marcadas por la impunidad, la no reparación y la percepción de indefensión, hace que la identidad del maestro, que está constituida por su propia historia personal, por la conciencia de su rol público, por la valoración social de su profesión, y por su definición política, producen diferentes formas de enunciación de sí mismos, a la vez que determinantes del tipo de actitud que se asuma como mecanismo de sobrevivencia. De esta manera se ubican la “NORMALIDAD” que lleva a la naturalización del horror y la violencia, la “INDIFERENCIA” que actúa como mecanismo de evasión, el “AISLAMIENTO” similar al anterior pero que se caracteriza por su rol de protección, los “ACTOS MIMÉTICOS” que se plantean como necesaria respuesta ante la polarización exigida por los distintos actores armados, “A LOS FIERROS” donde por definición ideológica o identificación con uno de los actores armados el maestro asume un involucramiento activo en la guerra, “EL TRASLADO” como búsqueda de escape para garantizar la vida ante la amenaza y la presión directas, y por último “A JUGÁRSELA” como respuesta desde el compromiso vital, político o religioso, y que lleva a continuar en la zona y actuando de acuerdo a sus principios a pesar del riesgo que ello implica.

Modelamiento geoestadístico de los depósitos fluviales de la zona c-formación mugrosa en el área la Cira-Este del Campo La Cira

OpenAIRE

Rojas Suárez, César Augusto

2011-01-01

Mediante algoritmos geoestadísticos se realizo el modelo tridimensional de los yacimientos fluviales de la Zona-C de la Formación Mugrosa en el área Cira-Este del Campo La Cira. Este modelo permitió calcular el aceite original en sitio e identificar las reservas que aun no han sido drenadas en el yacimiento. / Abstract. Geostatistical algorithms were used for making the three-dimensional model for the fluvial deposits of Zona-C of Mugrosa Formation in the Cira-Este area of the Cira Field. Thi...

Análisis de redes sociales para la gobernanza de un área protegida y su zona de amortiguación en el bosque templado del sur de Chile

OpenAIRE

Mardones, Gonzalo

2017-01-01

Para transitar desde el manejo hacia la gobernanza de las áreas protegidas y sus zonas aledañas, se requiere el involucramiento y la colaboración de las comunidades locales, además de múltiples otros actores involucrados en la conservación y el desarrollo de dicho territorio. El presente trabajo presenta un análisis de redes sociales de los actores con interés y/o influencia en la zona de amortiguación del Parque Nacional Alerce Andino (PNAA) y la Reserva Nacional Llanquihue (RNLL), ubicado e...

Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones.

Science.gov (United States)

Parkinson, Elizabeth I; Jason Hatfield, M; Tsurkan, Lyudmila; Hyatt, Janice L; Edwards, Carol C; Hicks, Latorya D; Yan, Bing; Potter, Philip M

2011-08-01

Carboxylesterases (CE) are ubiquitous enzymes found in both human and animal tissues and are responsible for the metabolism of xenobiotics. This includes numerous natural products, as well as a many clinically used drugs. Hence, the activity of these agents is likely dependent upon the levels and location of CE expression. We have recently identified benzil is a potent inhibitor of mammalian CEs, and in this study, we have assessed the ability of analogues of this compound to inhibit these enzymes. Three different classes of molecules were assayed: one containing different atoms vicinal to the carbonyl carbon atom and the benzene ring [PhXC(O)C(O)XPh, where X=CH₂, CHBr, N, S, or O]; a second containing a panel of alkyl 1,2-diones demonstrating increasing alkyl chain length; and a third consisting of a series of 1-phenyl-2-alkyl-1,2-diones. In general, with the former series of molecules, heteroatoms resulted in either loss of inhibitory potency (when X=N), or conversion of the compounds into substrates for the enzymes (when X=S or O). However, the inclusion of a brominated methylene atom resulted in potent CE inhibition. Subsequent analysis with the alkyl diones [RC(O)C(O)R, where R ranged from CH₃ to C₈H₁₇] and 1-phenyl-2-alkyl-1,2-diones [PhC(O)C(O)R where R ranged from CH₃ to C₆H₁₃], demonstrated that the potency of enzyme inhibition directly correlated with the hydrophobicity (clogP) of the molecules. We conclude from these studies that that the inhibitory power of these 1,2-dione derivatives depends primarily upon the hydrophobicity of the R group, but also on the electrophilicity of the carbonyl group. Copyright © 2011 Elsevier Ltd. All rights reserved.

Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition

Science.gov (United States)

Grieco, Steven F.; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S.; Beurel, Eléonore

2016-01-01

An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10 mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. PMID:27542584

Inhibiting the VIM-2 Metallo-β-Lactamase by Graphene Oxide and Carbon Nanotubes.

Science.gov (United States)

Huang, Po-Jung Jimmy; Pautler, Rachel; Shanmugaraj, Jenitta; Labbé, Geneviève; Liu, Juewen

2015-05-13

Metallo-β-lactamases (MBLs) degrade a broad spectrum of antibiotics including the latest carbapenems. So far, limited success has been achieved in developing its inhibitors using small organic molecules. VIM-2 is one of the most studied and important MBLs. In this work, we screened 10 nanomaterials, covering a diverse range of surface properties including charge, hydrophobicity, and specific chemical bonding. Among these, graphene oxide and carbon nanotubes are the most potent inhibitors, while most other materials do not show much inhibition effect. The inhibition is noncompetitive and is attributed to the hydrophobic interaction with the enzyme. Adsorption of VIM-2 was further probed using protein displacement assays where it cannot displace or be displaced by bovine serum albumin (BSA). This information is useful for rational design inhibitors for MBLs and more specific inhibition might be achieved by further surface modifications on these nanocarbons.

Intracellular alkalinization induces cytosolic Ca2+ increases by inhibiting sarco/endoplasmic reticulum Ca2+-ATPase (SERCA.

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Sen Li

Full Text Available Intracellular pH (pHi and Ca(2+ regulate essentially all aspects of cellular activities. Their inter-relationship has not been mechanistically explored. In this study, we used bases and acetic acid to manipulate the pHi. We found that transient pHi rise induced by both organic and inorganic bases, but not acidification induced by acid, produced elevation of cytosolic Ca(2+. The sources of the Ca(2+ increase are from the endoplasmic reticulum (ER Ca(2+ pools as well as from Ca(2+ influx. The store-mobilization component of the Ca(2+ increase induced by the pHi rise was not sensitive to antagonists for either IP(3-receptors or ryanodine receptors, but was due to inhibition of the sarco/endoplasmic reticulum Ca(2+-ATPase (SERCA, leading to depletion of the ER Ca(2+ store. We further showed that the physiological consequence of depletion of the ER Ca(2+ store by pHi rise is the activation of store-operated channels (SOCs of Orai1 and Stim1, leading to increased Ca(2+ influx. Taken together, our results indicate that intracellular alkalinization inhibits SERCA activity, similar to thapsigargin, thereby resulting in Ca(2+ leak from ER pools followed by Ca(2+ influx via SOCs.

Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Eskerod, O; Bukhave, K

1995-01-01

Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor...... antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue...... blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4...

Inhibition of PDGFR by CP-673451 induces apoptosis and increases cisplatin cytotoxicity in NSCLC cells via inhibiting the Nrf2-mediated defense mechanism.

Science.gov (United States)

Yang, Yang; Deng, Yanchao; Chen, Xiangcui; Zhang, Jiahao; Chen, Yueming; Li, Huachao; Wu, Qipeng; Yang, Zhicheng; Zhang, Luyong; Liu, Bing

2018-05-29

Platelet-derived growth factor receptors (PDGFRs) are abundantly expressed by stromal cells in the non-small cell lung cancer (NSCLC) microenvironment, and in a subset of cancer cells, usually with their overexpression and/or activating mutation. However, the effect of PDGFR inhibition on lung cancer cells themselves has been largely neglected. In this study, we investigated the anticancer activity of CP-673451, a potent and selective inhibitor of PDGFRβ, on NSCLC cell lines (A549 and H358) and the potential mechanism. The results showed that inhibition of PDGFRβ by CP-673451 induced a significant increase in cell apoptosis, accompanied by ROS accumulation. However, CP-673451 exerted less cytotoxicity in normal lung epithelial cell line BEAS-2B cells determined by MTT and apoptosis assay. Elimination of ROS by NAC reversed the CP-673451-induced apoptosis in NSCLC cells. Furthermore, CP-673451 down-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) probably through inhibition of PI3K/Akt pathway. Rescue of Nrf2 activity counteracted the effects of CP-673451 on cell apoptosis and ROS accumulation. Silencing PDGFRβ expression by PDGFRβ siRNA exerted similar effects with CP-673451 in A549 cells, and when PDGFRβ was knockdowned by PDGFRβ siRNA, CP-673451 produced no additional effects on cell viability, ROS and GSH production, Nrf2 expression as well as PI3K/Akt pathway activity. Specifically, Nrf2 plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and we found that combination of CP-673451 and cisplatin produced a synergistic anticancer effect and substantial ROS production in vitro. Therefore, these results clearly demonstrate the effectiveness of inhibition of PDGFRβ against NSCLC cells and strongly suggest that CP-673451 may be a promising adjuvant chemotherapeutic drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Brucella infection inhibits macrophages apoptosis via Nedd4-dependent degradation of calpain2.

Science.gov (United States)

Cui, Guimei; Wei, Pan; Zhao, Yuxi; Guan, Zhenhong; Yang, Li; Sun, Wanchun; Wang, Shuangxi; Peng, Qisheng

2014-11-07

The calcium-dependent protease calpain2 is involved in macrophages apoptosis. Brucella infection-induced up-regulation of intracellular calcium level is an essential factor for the intracellular survival of Brucella within macrophages. Here, we hypothesize that calcium-dependent E3 ubiquitin ligase Nedd4 ubiquitinates calpain2 and inhibits Brucella infection-induced macrophage apoptosis via degradation of calpain2.Our results reveal that Brucella infection induces increases in Nedd4 activity in an intracellular calcium dependent manner. Furthermore, Brucella infection-induced degradation of calpain2 is mediated by Nedd4 ubiquitination of calpain2. Brucella infection-induced calpain2 degradation inhibited macrophages apoptosis. Treatment of Brucella infected macrophages with calcium chelator BAPTA or Nedd4 knock-down decreased Nedd4 activity, prevented calpain2 degradation, and resulted in macrophages apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of Shiga Toxin 2 (Stx2) in Apple Juices and its Resistance to Pasteurization

Science.gov (United States)

In the present study, we evaluated Shiga toxin (Stx2) activity in apple juices by measuring a decrease in dehydrogenase activity of Vero cells with the microculture tetrazolium (MTT) assay. Freshly prepared juice from Red Delicious apples and Golden Delicious apples inhibited the biological activity...

Trastornos Asociados a la Deficiencia de Yodo. Vigilancia permanente es deficitaria en zonas vulnerables

Directory of Open Access Journals (Sweden)

Hernando Vargas-Uricoechea

2012-04-01

Full Text Available Los Desórdenes por Deficiencia de Yodo (DDY son uno de los mayores problemas en salud pública en el mundo actual, en especial en niños y embarazadas. Estos trastornos truncan el desarrollo socioeconómico en aquellas zonas que los padecen; las poblaciones que viven en zonas yodo-deficientes siempre van a estar expuestas a sufrir las consecuencias originadas por esta deficiencia, en especial el aumento en la mortalidad perinatal, retardo mental, alteraciones en la síntesis de hormonas tiroideas, hipotiroidismo, hipertiroidismo y bocio. La mejor forma de evaluar los DDY es por medio de la yoduria y la mejor estrategia para reducir la prevalencia de estos desórdenes en la población es a través de la yodación universal de la sal. Para actualizar el conocimiento de esta problemática –tanto en el mundo como en Colombia- se realizó una revisión sistemática de la literatura médica expuesta en las bases de datos de MEDLINE y de LILACS. En total, la búsqueda arrojó la presencia de 723 artículos, la revisión de sus resúmenes permitió escoger inicialmente 114 artículos, de los cuales se decidió incluir en la revisión a 60 de ellos. Se encontró que en Colombia el diagnóstico de DDI es subvalorado, desconociéndose la problemática actual y el estado del yodo poblacional, por lo que es necesario realizar estos estudios, ya que es evidente el abandono político de este problema prevenible, predecible y tratable.

Inhibition by 2-deoxy-D-ribose of DNA synthesis and growth in Raji cells

International Nuclear Information System (INIS)

Ulrich, F.

1988-01-01

When Raji cells were cultured for 3 days in serum-free medium, addition of 2-deoxy-D-ribose at the start of culture inhibited incorporation of [ 3 H]thymidine and cell division. At deoxyribose concentrations between 1 and 5 mM, viability was 80% or greater after 3 days of culture even though 5 mM deoxyribose inhibited thymidine incorporation 95-99%. Inhibition by deoxyribose could be completely reversed if the culture medium was replaced with fresh medium up to 8 hr after the start of culture. The inhibition was specific for deoxyribose since other monosaccharides had no effect. Inhibition of DNA synthesis did not appear to be due to depletion of essential nutrients in the medium since the percentage inhibition of thymidine incorporation by cells cultured either in suboptimal serum-free media or in media supplemented with 0.025-5% human AB serum was similar. When DNA repair synthesis was measured as hydroxyurea-resistant thymidine incorporation, addition of deoxyribose to Raji cultures caused increased thymidine incorporation. These results, together with data from others,suggest that deoxyribose damages DNA

Seroprevalencia de la enfermedad de Chagas en Ushuaia, Argentina, una zona sin triatominos

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Mallimaci María Cristina

2001-01-01

Full Text Available Objetivos. Determinar la seroprevalencia de la infección por Trypanosoma cruzi en Ushuaia, la ciudad más austral del mundo. Métodos. Se analizaron muestras de suero de 2 991 personas, obtenidas entre enero de 1995 y diciembre de 1996. Las muestras fueron procesadas por hemaglutinación indirecta (HAI e inmunoensayo enzimático (ELISA o inmunofluorescencia indirecta (IFI. Resultados. La seroprevalencia general de la infección por T. cruzi fue de 6,8%. La prevalencia según el país de origen fue de 41,1% en los bolivianos, 5,0% en los argentinos y 0,9% en los chilenos; en embarazadas fue de 5,9%, en exámenes obligatorios de 6,3% y en consultas dirigidas de 30,8%. Conclusiones. Se destaca la magnitud de la infección por T. cruzi en una zona donde no existe el insecto vector. Debido al riesgo de la transmisión congénita y transfusional, es necesario mantener el control de la sangre a transfundir y reforzar el seguimiento de los hijos de mujeres infectadas para un diagnóstico precoz y tratamiento oportuno de la infección.

EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

Directory of Open Access Journals (Sweden)

Zhan-Li Shi

2018-01-01

Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

Zonas de clandestinidad y “nuda vida:” Mujeres, cuerpo y aborto

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Barbara Sutton

2017-05-01

producción de cuerpos ocultos (particularmente de mujeres que son expuestos al peligro y que pueden ser “matados” con impunidad? ¿Es el control violento de estos cuerpos invisibles/excluidos un requisito para mantener intacta la ilusión de la unidad del cuerpo del Estado soberano? Prestar atención a las zonas de clandestinidad que persisten en los Estados democráticos puede ayudar a arrojar luz no sólo sobre las precarias formas de ciudadanía de las personas que integran el cuerpo político de manera marginal, sino también sobre las intervenciones violentas, pero ocultas, por las cuales el Estado soberano mantiene su poder y las jerarquías de género en que se asienta.

Investigación de un foco de leishmaniasis cutánea en la zona andina del departamento de Nariño

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César G. Arroyo

1996-01-01

Full Text Available En el municipio de Samaniego, ubicado en la zona andina del departamento de Nariño, se detectaron 14 casos de leismaniasis cutánea entre 1992 y 1995, presentándose 13 de ellos (93% en niños menores de 13 años. En todos, las lesiones se localizaron en la cara. En tres de los casos se pudieron tipificar las cepas, correspondiendo a L. mexicana, resultado que coincide con la tipificación del primer paciente encontrado en Samaniego en 1984 y primer caso de leishmaniasis cutánea anérgica difusa informado en Colombia. Paralelamente, se identificaron las especies de flebotomíneos recolectados en la zona, correspondiendo todos a Lutzomya columbiana (grupo verrucarum, hallazgo que concuerda con varios informes anteriores de la misma región desde 1940, cuando se buscaba el vector de la epidemia de bartonelosis en esta zona nariñense, hasta 1984 cuando el INS realizó muestreos a raíz del mencionado caso de leishmaniasis difusa encontrado por nosotros en ese municipio. Aunque no se logró demostrar infección natural en los 400 flebotomíneos capturados, sí se consiguió infectar algunos especímenes de Lutzomya columbiana, expuestos a hámsteres inoculados con la cepa de L. mexicana aislada de un paciente incluido en el estudio. Por este hallazgo y por la evidencia epidemiológica, se incrimina a Lutzomya columbiana como posible trasmisor de L. mexicana, vector que hasta la fecha no había sido involucrado en la trasmisión de leishmania. Todos los pacientes estudiados respondieron al tratamiento convencional con glucantime®.

Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase.

Science.gov (United States)

Joshi, Vikram; Umashankara, M; Ramakrishnan, Chandrasekaran; Nanjaraj Urs, Ankanahalli N; Suvilesh, Kanve Nagaraj; Velmurugan, Devadasan; Rangappa, Kanchugarakoppal S; Vishwanath, Bannikuppe Sannanaik

2016-05-15

Overproduction of arachidonic acid (AA) mediated by secretory phospholipase A2 group IIA (sPLA2IIA) is a hallmark of many inflammatory disorders. AA is subsequently converted into pro-inflammatory eicosanoids through 5-lipoxygenase (5-LOX) and cyclooxygenase-1/2 (COX-1/2) activities. Hence, inhibition of sPLA2IIA, 5-LOX and COX-1/2 activities is critical in regulating inflammation. We have previously reported unconjugated bilirubin (UCB), an endogenous antioxidant, as sPLA2IIA inhibitor. However, lipophilic UCB gets conjugated in liver with glucuronic acid into hydrophilic conjugated bilirubin (CB). Since hydrophobicity is pre-requisite for sPLA2IIA inhibition, conjugation reduces the efficacy of UCB. In this regard, UCB was chemically modified and derivatives were evaluated for sPLA2IIA, 5-LOX and COX-1/2 inhibition. Among the derivatives, BD1 (dimethyl ester of bilirubin) exhibited ∼ 3 fold greater inhibitory potency towards sPLA2IIA compared to UCB. Both UCB and BD1 inhibited human 5-LOX and COX-2 activities; however only BD1 inhibited AA induced platelet aggregation. Molecular docking studies demonstrated BD1 as better inhibitor of aforesaid enzymes than UCB and other endogenous antioxidants. These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance. Copyright © 2016 Elsevier Inc. All rights reserved.

Metal pollution (Pb, Zn, Ni and Cr) in air, road and soil sediment in a high traffic area; Contaminacion por metales (Pb, Zn, Ni y Cr) en aire, sedimentos viales y suelo en una zona de alto trafico vehicular

Energy Technology Data Exchange (ETDEWEB)

Manchado, Anali; Garcia, Neyma; Garcia, Cezar; Acosta, Lorena; Cordova, Alberto; Linares, Maria; Giraldoth, Debora [Centro de Investigaciones CEDEGAS, Facultad de Ingenieria, Universidad del Zulia, Maracaibo (Venezuela)]. E-mail: analimachado@yahoo.com; amachadop@luz.edu.ve; Velasquez, Harvi [Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo (Venezuela)

2008-11-15

sequia y de lluvia, empleando un muestreador de bajo volumen con filtros de fibra de cuarzo -para las muestras de PM10- con una frecuencia de una muestra cada tres dias para un total de 26; para los sedimentos viales y suelo fueron colectadas tres muestras con una frecuencia de 15 dias para un periodo de medicion de mes y medio en epoca seca. Todas las muestras fueron sometidas a un proceso de digestion y analizadas por espectrometria de absorcion atomica. Las concentraciones de las PM10 resultaron 2 veces mas altas en la zona de emision que en la zona de dispersion durante ambas epocas climatologicas, presentando una mejor correlacion entre las zonas para epoca de sequia. Todos los metales analizados presentaron diferencias estadisticamente significativas entre las zonas de muestreo. Por otra parte, para el periodo global existen diferencias significativas entre las zonas y las epocas climatologicas tanto para PM10 como para la totalidad de los metales. El Pb no excedio el estandar de calidad del aire establecido para Venezuela, pero su concentracion promedio en la zona de emision fue de 1.13 {mu}g/m{sup 3}, muy cercano al limite diario permitido en Venezuela y por la EPA; por su parte, tanto Pb como Ni sobrepasaron el limite permisible de la Organizacion Mundial de la Salud (OMS) en ambas zonas durante todo el periodo de muestreo. Para las muestras de sedimento y de suelo se encontraron concentraciones significativamente elevadas de Pb, Zn, Ni y Cr en comparacion con la muestra testigo. Los niveles hallados de Pb y Zn estan por encima de los limites permitidos por el decreto 2635 de la normativa venezolana y la EPA, clasificandose la zona como suelo con alta contaminacion por metales pesados. Adicionalmente, el analisis estadistico demostro la adecuada seleccion de la zona de monitoreo, confirmando que la principal fuente de emision de los contaminantes es el parque automotor.

Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes.

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Pabbidi, M R; Ji, X; Maxwell, J T; Mignery, G A; Samarel, A M; Lipsius, S L

2016-01-01

We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in-PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in-PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In-PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in-PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of �

Cyclooxygenase-2 Inhibition Enhances Proliferation of NKT Cells Derived from Patients with Laryngeal Cancer.

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Klatka, Janusz; Grywalska, Ewelina; Hymos, Anna; Guz, Małgorzata; Polberg, Krzysztof; Roliński, Jacek; Stepulak, Andrzej

2017-08-01

The aim of this study was to analyze whether inhibition of cyclooxygenase-2 by celecoxib and the subsequent enhancement in the proliferation of natural killer T (NKT) cells could play a role in dendritic cell (DC)-based laryngeal cancer (LC) immunotherapy. Peripheral blood mononuclear cells were obtained from 48 male patients diagnosed with LC and 30 control patients without cancer disease. Neoplastic cell lysate preparations were made from cancer tissues obtained after surgery and used for in vitro DCs generation. NKT cells proliferation assay was performed based on 3 H-thymidine incorporation assay. An increased proliferation of NKT cells was obtained from control patients compared to NKT cells obtained from LC patients regardless of the type of stimulation or treatment. In the patient group diagnosed with LC, COX-2 inhibition resulted in a significantly enhanced proliferation of NKT cells when stimulated with autologous DCs than NKT cells stimulated with DCs without COX-2 inhibition. These correlations were not present in the control group. Higher proliferation rate of NKT cells was also observed in non-metastatic and highly differentiated LC, which was independent of the type of stimulation or treatment. COX-2 inhibition could be regarded as immunotherapy-enhancing tool in patients with LC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Demanda de gasolina en la zona metropolitana del Valle de México: análisis empírico de la reducción del subsidio

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Jimy Ferrer Carbonell

2014-10-01

Full Text Available Este artículo analiza la demanda de gasolina en la Zona Metropolitana del Valle de México (ZMVM. Se modela el consumo de gasolina como una función del ingreso y el precio relativo. Utilizando el enfoque de cointegración se encuentra una relación estable y de largo plazo entre las variables, que indica que la respuesta de la demanda es mayor ante cambios en el ingreso que frente a cambios en el precio, por lo que las políticas públicas basadas solo en precios no son suficientes para disminuir el consumo de gasolina en esta zona metropolitana, sino que estas deben complementarse con medidas de regulación.

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

Science.gov (United States)

Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

2018-03-24

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

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MPF Janssen

2017-10-01

Full Text Available Many studies have reported on the effects of cyclooxygenase-2 (COX-2 inhibition on osteogenesis. However, far less is known about the effects of COX-2 inhibition on chondrogenic differentiation. Previous studies conducted by our group show that COX-2 inhibition influences in vitro chondrogenic differentiation. Importantly, this might have consequences on endochondral ossification processes occurring in vivo, such as bone fracture healing, growth plate development and ectopic generation of cartilage. The goal of our study was to investigate, in vivo, the effect of COX-2 inhibition by celecoxib on the cartilaginous phase of three different endochondral ossification scenarios. 10 mg/kg/day celecoxib or placebo were orally administered for 25 d to skeletally-immature New Zealand White rabbits (n = 6 per group. Endochondral ossification during fracture healing of a non-critical size defect in the ulna, femoral growth plate and ectopically-induced cartilaginous tissue were examined by radiography, micro-computed tomography (µ-CT, histology and gene expression analysis. Celecoxib treatment resulted in delayed bone fracture healing, alterations in growth plate development and progression of mineralisation. In addition, chondrogenic differentiation of ectopically-induced cartilaginous tissue was severely impaired by celecoxib. In conclusion, we found that celecoxib impaired the chondrogenic phase of endochondral ossification.

Microanatomical diversification of the zona pellucida in aplochelioid killifishes.

Science.gov (United States)

Thompson, A W; Furness, A I; Stone, C; Rade, C M; Ortí, G

2017-07-01

This study investigates zona pellucida (ZP) ultrastructure in fertilized eggs of annual killifishes (suborder Aplocheiloidei), a group of highly specialized fishes that are able to survive desiccation for several weeks to months before they hatch. Little is known about ZP or chorionic ultrastructure sustaining these life-history modes, so scanning electron microscopy (SEM) was used to describe this trait in a large number of aplocheiloids with a focus on the family Rivulidae and the genus Hypsolebias. New images of ZP ultrastructure for 52 aplocheiloid species are provided, more than doubling the number characterized thus far. The evolution of chorionic structure within this group is studied using these new data. Characters were coded into a morphological matrix and optimized onto a consensus phylogeny to assess phylogenetic signal and reconstruct ancestral character states. Although ZP characters seem highly homoplastic and exhibit a large amount of structural convergence among lineages, aplocheiloid killifishes have evolved a number of unique structures associated with the chorion. Some annual species seem to have lost long filaments because eggs are deposited in the soil instead of being adhered to aquatic plants. © 2017 The Fisheries Society of the British Isles.

Inhibition by AA861 of prostaglandin E2 production by activated peritoneal macrophages of rat

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Ohuchi, K; Watanabe, M; Taniguchi, J; Tsurufuji, S; Levine, L

1983-10-01

Prostaglandin E2 production by rat peritoneal activated macrophages was inhibited by AA861 which had been reported as a selective inhibitor of 5-lipoxygenase from guinea pig peritoneal leukocytes. At a dose of 3.06 microM, prostaglandin E2 production was decreased to 27% of control. No inhibition of the release of (3H)arachidonic acid from the prelabeled macrophages was observed at the dose.

Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation.

Science.gov (United States)

Fridman, Jordan S; Scherle, Peggy A; Collins, Robert; Burn, Timothy; Neilan, Claire L; Hertel, Denise; Contel, Nancy; Haley, Patrick; Thomas, Beth; Shi, Jack; Collier, Paul; Rodgers, James D; Shepard, Stacey; Metcalf, Brian; Hollis, Gregory; Newton, Robert C; Yeleswaram, Swamy; Friedman, Steven M; Vaddi, Kris

2011-09-01

JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis (AD). Direct antagonism of cytokines, such as IL-12 and IL-23 using ustekinumab, has proven effective in randomized studies in psoriasis patients. We hypothesized that local inhibition of cytokine signaling using topical administration of INCB018424, a small molecule inhibitor of JAK1 and JAK2, would provide benefit similar to systemic cytokine neutralization. In cellular assays, INCB018424 inhibits cytokine-induced JAK/signal transducers and activators of transcription (STAT) signaling and the resultant production of inflammatory proteins (e.g., IL-17, monocyte chemotactic protein-1, and IL-22) in lymphocytes and monocytes, with half-maximal inhibitory concentration values keratinocyte proliferation in a murine contact hypersensitivity model and inhibited tissue inflammation induced by either intradermal IL-23 or TSLP. Topical INCB018424 was also well tolerated in a 28-day safety study in Gottingen minipigs. These results suggest that localized JAK1/JAK2 inhibition may be therapeutic in a range of inflammatory skin disorders such as psoriasis and AD. Clinical evaluation of topical INCB018424 is ongoing.

Herb–drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7

Energy Technology Data Exchange (ETDEWEB)

Ma, Hai-Ying [The Fourth Affiliated Hospital of China Medical University, Shenyang 110032 (China); Sun, Dong-Xue [School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016 (China); Cao, Yun-Feng [The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Ai, Chun-Zhi [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Qu, Yan-Qing [Thyroid Surgery, Yantaishan Hospital, Yantai, Shandong (China); Hu, Cui-Min [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057 (United States); Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); Dong, Pei-Pei [Academy of Integrative Medicine, Dalian Medical University, Dalian 116044 (China); Sun, Xiao-Yu; Hong, Mo [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Tanaka, Naoki; Gonzalez, Frank J. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); others, and

2014-05-15

Herb–drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (K{sub i}) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (K{sub i}) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb–drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. - Highlights: • Specific inhibition of andrographolide derivatives towards UGT2B7. • Herb-drug interaction related withAndrographis paniculata. • Guidance for design of UGT2B7 specific inhibitors.

Herb–drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7

International Nuclear Information System (INIS)

Ma, Hai-Ying; Sun, Dong-Xue; Cao, Yun-Feng; Ai, Chun-Zhi; Qu, Yan-Qing; Hu, Cui-Min; Jiang, Changtao; Dong, Pei-Pei; Sun, Xiao-Yu; Hong, Mo; Tanaka, Naoki; Gonzalez, Frank J.

2014-01-01

Herb–drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (K i ) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (K i ) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb–drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. - Highlights: • Specific inhibition of andrographolide derivatives towards UGT2B7. • Herb-drug interaction related withAndrographis paniculata. • Guidance for design of UGT2B7 specific inhibitors

Herb–drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7

Energy Technology Data Exchange (ETDEWEB)

Ma, Hai-Ying, E-mail: cmu4h-mhy@126.com [The Fourth Affiliated Hospital of China Medical University, Shenyang 110032 (China); Sun, Dong-Xue [School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016 (China); Cao, Yun-Feng [The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Ai, Chun-Zhi [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Qu, Yan-Qing [Thyroid Surgery, Yantaishan Hospital, Yantai, Shandong (China); Hu, Cui-Min [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057 (United States); Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); Dong, Pei-Pei [Academy of Integrative Medicine, Dalian Medical University, Dalian 116044 (China); Sun, Xiao-Yu; Hong, Mo [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Tanaka, Naoki; Gonzalez, Frank J. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); and others

2014-05-15

Herb–drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (K{sub i}) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (K{sub i}) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb–drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. - Highlights: • Specific inhibition of andrographolide derivatives towards UGT2B7. • Herb-drug interaction related withAndrographis paniculata. • Guidance for design of UGT2B7 specific inhibitors.

Effect of inhibition of microsomal Ca(2+)-ATPase on cytoplasmic calcium and enzyme secretion in pancreatic acini.

Science.gov (United States)

Metz, D C; Pradhan, T K; Mrozinski, J E; Jensen, R T; Turner, R J; Patto, R J; Gardner, J D

1994-01-13

We used thapsigargin (TG), 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ) and cyclopiazonic acid (CPA), each of which inhibits microsomal Ca(2+)-ATPase, to evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+]i) and secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single-cell microspectrofluorimetry of fura-2-loaded acini we found that all three agents caused a sustained increase in [Ca2+]i by mobilizing calcium from inositol-(1,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting influx of extracellular calcium. Concentrations of all three agents that increased [Ca2+]i potentiated the stimulation of enzyme secretion caused by secretagogues that activate adenylate cyclase but inhibited the stimulation of enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ, potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately whereas inhibition of phospholipase C-mediated enzyme secretion occurred only after several min of incubation. In addition, the effects of BHQ and CPA on both [Ca2+]i and secretagogue-stimulated enzyme secretion were reversed completely by washing whereas the actions of TG could not be reversed by washing. Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+]i inhibited all modes of stimulated enzyme secretion by a mechanism that was apparently unrelated to changes in [Ca2+]i. Finally, in contrast to the findings with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range of concentrations that was at least 10-fold lower than the range of concentrations over which CPA potentiated VIP-stimulated enzyme secretion.

Downregulation of TGF-β Receptor-2 Expression and Signaling through Inhibition of Na/K-ATPase.

Directory of Open Access Journals (Sweden)

Jennifer La

Full Text Available Transforming growth factor-beta (TGF-β is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-β signals through a complex of TGF-β receptors 1 and 2 (TGFβR1 and TGFβR2 that phosphorylate and activate Smad2/3 transcription factors driving transcription of the Smad-target genes. The Na+/K+-ATPase is an integral plasma membrane protein critical for maintaining the electro-chemical gradient of Na+ and K+ in the cell. We found that inhibition of the Na+/K+ ATPase by ouabain results in a dramatic decrease in the expression of TGFβR2 in human lung fibrobalsts (HLF at the mRNA and protein levels. This was accompanied by inhibition of TGF-β-induced Smad phosphorylation and the expression of TGF-β target genes, such as fibronectin and smooth muscle alpha-actin. Inhibition of Na+/K+ ATPase by an alternative approach (removal of extracellular potassium had a similar effect in HLF. Finally, treatment of lung alveolar epithelial cells (A549 with ouabain also resulted in the downregulation of TGFβR2, the inhibition of TGF-β-induced Smad phosphorylation and of the expression of mesenchymal markers, vimentin and fibronectin. Together, these data demonstrate a critical role of Na+/K+-ATPase in the control of TGFβR2 expression, TGF-β signaling and cell responses to TGF-β.

SISTEMAS DE GESTIÓN AMBIENTAL EN LOS LABORATORIOS FOTOGRÁFICOS PyMES DE LAS ZONAS DE CHAPINERO Y SANTAFÉ EN BOGOTÁ D.C.

Directory of Open Access Journals (Sweden)

Nury Zaride Alfonso Ávila

2003-07-01

Full Text Available Los sistemas de gestión ambiental permiten a las empresas involucrar la variable ambiental de una forma sistemática y ordenada. Este artículo da a conocer en forma resumida algunos de los resultados obtenidos en la investigación desarrollada en los laboratorios fotográficos de las zonas 2 y 3 de la ciudad de Bogotá. Es evidente la necesidad de involucrar en los procesos de producción la variable ambiental y verificar el cumplimiento de la norma ISO 14000, uno de los modelos más conocidos en el mundo.

Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

Science.gov (United States)

Shin, Hyewon; Song, Jin-Ho

2014-09-05

Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases

DEFF Research Database (Denmark)

Theander, T G; Kharazmi, A; Pedersen, B K

1988-01-01

This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference...... in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess......, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment...

Invernaderos sostenibles para la producción de hortalizas en zonas alto andinas del Cusco

OpenAIRE

Zanabria Pacheco, Pedro Fortunato

2015-01-01

La investigación tiene como objetivo determinar la importancia en el uso de los invernaderos sostenibles para la producción de hortalizas en las zonas alto andinas del Curso. Para ello, se han diseñado y construido dos prototipos de invernaderos a 3330 msnm, variando la orientación y forma del techo, permitiendo la producción de hortalizas en la estación fría. A la vez está investigación servirá como base para aplicar el proyecto sobre la tecnología de producción sostenible de hortalizas bajo...

Brucelosis: condición socioeconómica familiar y calidad de vida en dos zonas contrastantes del estado de Tlaxcala, México

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Guillermina García Juárez

2013-01-01

Full Text Available La brucelosis, o fiebre de Malta, es una enfermedad zoonótica ocasionada por la bacteria intracelular del género Brucella melitensis y Brucella abortus. En el estado de Tlaxcala los caprinos son los principales reservorios y los productos lácteos no pasteurizados ocasionan daños a la salud pública. En el año 2008 se presentó una tasa de morbilidad de 4.78/100000 habitantes, con ello se ocupó el cuarto lugar a nivel nacional; al segundo bimestre del 2011 se pasó al primer lugar nacional. El objetivo del estudio fue analizar la condición socioeconómica familiar de los individuos afectados con brucelosis en las zonas rural y urbana, evaluando la calidad de vida. Los grupos de estudio fueron seleccionados por regionalización a través del programa Arc View-3.2. Se aplicaron dos cuestionarios con los siguientes propósitos: 1 analizar la condición socioeconómica de los grupos de estudio y 2medir la calidad de vida en los individuos infectados y sanos, empleando el método de Rand Group. Los resultados mostraron que en la zona rural, de baja condición socioeconómica, había mayor incidencia de brucelosis, interrupción en tratamientos médicos, complicaciones médicas en los individuos enfermos, menor nivel educativo, menos servicios médicos y medicamentos. La calidad de vida de los individuos infectados con brucelosis fue menor, cuando se comparó con los grupos de individuos sanos.

Corrosion Inhibition in the Secondary Cooling System of ETRR-2, Egypt

International Nuclear Information System (INIS)

Aly, A.H.; Gad, M.M.A.; Abdel-Karim, R.; Abdel-Salam, O.F.

2003-01-01

The second Egyptian research reactor (ETRR-2) is a light water type of 22 MW thermal power. Proper cooling water treatment is necessary to set the water chemical characteristics within a specified window to avoid or minimize corrosion problems, scale formation, fouling, and microbiological contamination. Selection of a proper and economic corrosion inhibitor is of great importance. This selection depends, among other factors, on the availability as well as cost. The corrosion behaviour of water of ETRR-2 site and its inhibition by different inhibitors was studied in a special test rig designed for this purpose. Sodium salts of polyphosphate, phosphate, molybdate, and tungstate were used to treat and qualify the cooling water. Results showed that the corrosion resistance of the test material depends on both type and concentration of the applied inhibitor. Using 30-ppm tungstate, molybdate, and phosphate (as anodic inhibitors) reduced the corrosion rate, and inhibitor efficiencies of about 97% 86%, and 68% were achieved respectively. Accordingly, sodium tungstate could be ranked as the best anodic inhibitor used followed by molybdate. Sodium phosphate could be ranked as the least efficient one. Adding the same concentration of sodium polyphosphate (as a cathodic inhibitor) yields almost the same inhibition efficiency as tungstate type. However, at higher concentration(40 ppm), an inhibition efficiency of 100% was obtained, Which corresponds to almost zero-corrosion rate

Data in support of the negative influence of divalent cations on (?)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2)

OpenAIRE

Deb, Gauri; Batra, Sahil; Limaye, Anil M.

2015-01-01

In this data article we have provided evidence for the negative influence of divalent cations on (−)‐epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2.

Palma de aceite y desplazamiento forzado en Zona Bananera: “trayectorias” entre recursos naturales y conflicto.

Directory of Open Access Journals (Sweden)

Juanita Goebertus Estrada.

2008-06-01

Full Text Available This article describes the mechanisms through which the transition from banana to oil palm plantations in Zona Bananera, Magdalena, has been influential in forced displacement. Therefore it adds to the debate about the paths between resources and conflict in the literature on political economy of internal armed conflicts. The outcome of this qualitative research suggests that in the case in question the following “pathways” have operated: 1. The absence of a strong institutional presence has permitted the collection of extortions by illegal armed groups allowing their financing and generating forced displacement as a consequence of the threats; 2. The transition from banana to palm extraction reduced the intensity of manual labor and food security unleashing displacement processes; and 3. The institutional incentives for oil palm exploitation have promoted the usurpation of land by illegal armed actors who provoke the displacement in order to acquire land for their cultivation.

Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.

Science.gov (United States)

Zhang, Yafei; Zhang, Bicheng; Zhang, Anran; Zhao, Yong; Zhao, Jie; Liu, Jian; Gao, Jianfei; Fang, Dianchun; Rao, Zhiguo

2012-09-01

Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients

Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

Science.gov (United States)

Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

2012-01-01

Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

Curcumin Inhibits Growth of Human NCI-H292 Lung Squamous Cell Carcinoma Cells by Increasing FOXA2 Expression

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Lingling Tang

2018-02-01

Full Text Available Lung squamous cell carcinoma (LSCC is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6 significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways.

Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.

Science.gov (United States)

Hockey, Leanne N; Kilpatrick, Bethan S; Eden, Emily R; Lin-Moshier, Yaping; Brailoiu, G Cristina; Brailoiu, Eugen; Futter, Clare E; Schapira, Anthony H; Marchant, Jonathan S; Patel, Sandip

2015-01-15

Two-pore channels (TPCs) are endolysosomal ion channels implicated in Ca(2+) signalling from acidic organelles. The relevance of these ubiquitous proteins for human disease, however, is unclear. Here, we report that lysosomes are enlarged and aggregated in fibroblasts from Parkinson disease patients with the common G2019S mutation in LRRK2. Defects were corrected by molecular silencing of TPC2, pharmacological inhibition of TPC regulators [Rab7, NAADP and PtdIns(3,5)P2] and buffering local Ca(2+) increases. NAADP-evoked Ca(2+) signals were exaggerated in diseased cells. TPC2 is thus a potential drug target within a pathogenic LRRK2 cascade that disrupts Ca(2+)-dependent trafficking in Parkinson disease. © 2015. Published by The Company of Biologists Ltd.

Topical W-7 inhibits ultraviolet radiation-induced melanogenesis in Skh:HR2 pigmented hairless mice

International Nuclear Information System (INIS)

Dowdy, J.C.; Anthony, F.A.; Costlow, M.E.

1995-01-01

We studied the effect of N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7) on ultraviolet radiation (UVR)-induced melanogenesis (tanning) in Skh:HR2 pigmented hairless mice. Topically pretreated mice were exposed to subminimal edematogenic as well as edematogenic UVR doses to establish whether W-7-UVR-induced edema prophylaxis allows increased melanogenesis while preventing edema. Ultraviolet light-irradiated vehicle control animals developed visible trans; however, both W-7-treated groups failed to tan. Topical W-7 before UVR exposure inhibited UVR induction of dopa oxidase activity in melanocytes by 49% (P=0.029) and inhibited UVR-induced deposition of melanin in the epidermis by 88% (P=0.006). Topical W-7 blocked 23% of the UVR but this blockage could not account for the inhibition of dopa oxidase and melanization. We conclude that, in addition to preventing edema, W-7 inhibits UVR-induced melanogenesis, possibly by affecting Ca 2+ -calmodulin and/or protein kinase C-dependent processes. (au) 30 refs

Topical W-7 inhibits ultraviolet radiation-induced melanogenesis in Skh:HR2 pigmented hairless mice

Energy Technology Data Exchange (ETDEWEB)

Dowdy, J.C. [Univ. of Memphis, Div. of Molecular Sciences and Microbiology, Memphis, Tennessee (United States); Anthony, F.A.; Costlow, M.E. [Schering-Plough HealthCare Products, Inc., Advanced Product Research, Memphis, Tennessee (United States)

1995-08-01

We studied the effect of N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7) on ultraviolet radiation (UVR)-induced melanogenesis (tanning) in Skh:HR2 pigmented hairless mice. Topically pretreated mice were exposed to subminimal edematogenic as well as edematogenic UVR doses to establish whether W-7-UVR-induced edema prophylaxis allows increased melanogenesis while preventing edema. Ultraviolet light-irradiated vehicle control animals developed visible trans; however, both W-7-treated groups failed to tan. Topical W-7 before UVR exposure inhibited UVR induction of dopa oxidase activity in melanocytes by 49% (P=0.029) and inhibited UVR-induced deposition of melanin in the epidermis by 88% (P=0.006). Topical W-7 blocked 23% of the UVR but this blockage could not account for the inhibition of dopa oxidase and melanization. We conclude that, in addition to preventing edema, W-7 inhibits UVR-induced melanogenesis, possibly by affecting Ca{sup 2+}-calmodulin and/or protein kinase C-dependent processes. (au) 30 refs.

Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

Energy Technology Data Exchange (ETDEWEB)

Muchir, Antoine, E-mail: a.muchir@institut-myologie.org [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Wu, Wei [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Sera, Fusako; Homma, Shunichi [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Worman, Howard J., E-mail: hjw14@columbia.edu [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States)

2014-10-03

Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna{sup H222P/H222P} mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna{sup H222P/H222P} mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna{sup H222P/H222P} mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna{sup H222P/H222P} mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left

Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

International Nuclear Information System (INIS)

Muchir, Antoine; Wu, Wei; Sera, Fusako; Homma, Shunichi; Worman, Howard J.

2014-01-01

Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna H222P/H222P mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna H222P/H222P mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna H222P/H222P mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna H222P/H222P mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left ventricular fractional

Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction

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